Season Premiere. Abby, Carter, Chen, Pratt, and Stan will be confined to the ER for two weeks, while all of the other patients are evacuated and sent to different hospitals. While on the roof arguing with Luka about the use of a helicopter, Romano backs up into the tail rotor, and has his arm severed above the elbow. Anspaugh arrives to perform surgery, and reattaches the arm. Susan is stuck on the roof with a dying patient. After 2 weeks, the ER reopens. While all of this has been going on, Elizabeth has been in London, working at her father's hospital, where her supervisor doesn't like the American mannerisms and vocabulary she's picked up. She ultimately decides to return to Chicago.
Two months after the lockdown, a new group of med students arrives in the ER to pandemonium, caused by the closure of another city ER. Corday returns to the ER, having lost some of her beside manner. Gallant is on a psych rotation, all the while annoying the ER staff. Romano continues physical therapy. Weaver is acting strangely, and breaks down and cries in front of Elizabeth. Pratt brings a man, pronounced dead, back to life which infuriates Kayson.
Lewis treats an end-stage Huntington's patient, whose mother has already watched her husband wither from the disease. Abby's brother Eric, an Air Force traffic controller, visits on his way to a new post in Nebraska. Carter tends to a 12-year-old drug-addicted prostitute with a serious STD, until her pimp shows up and whisks her away. Pratt aggravates a drug-seeking man who comes back brandishing a gun at Chen and Abby and demanding Demerol. Abby gives him his shot but purposefully ODs him. In the aftermath, Carter flips his lid, demanding better security and the installation of metal detectors. When Weaver refuses, Carter leads a walkout. Weaver eventually caves, albeit before telling Carter that he must fire three senior nurses by the next morning to make up the expense. Abby, Lewis and Chen go to a concert to decompress.
Gallant has a rough day due to his inability to make himself heard. First, Pratt butts in on a patient of his. Then Stella Willis dies because Kayson didn't bother with thorough treatment. Weaver makes a mistake on live television while demonstrating flu shots, inadvertently sticking two reporters with the same needle. In the bathroom, Susan and Abby catch Weaver in a stall with a needle. Weaver later confesses to Susan that she's taking hormones. Carter, assuming Susan already knows, tells her about Abby's drinking problem. Abby becomes nurse manager, and argues with Carter about her drinking. Luka flirts with a patient's mom and is caught emerging from a storage closet with her.
On a busy Halloween night, Carter and Abby are the only staffers in costume when victims of an apartment building fire pack the ER. Corday takes on a new med student for a surgical rotation -- Paul Nathan, who suffers from Parkinson's disease and decided to pursue medicine after being diagnosed. Despite a difficult first day, both professionally and medically, Nathan makes a difficult diagnosis. Romano's rehab lags behind his expectations, and he begins to doubt his role in surgery is no longer an option. In a moment of personal weakness, he tries to express his feelings for Corday. Weaver continues to display erratic behavior, raising staff suspicions about her menopause. Luka's burgeoning sex addiction worsens, as an affair with Chuny is revealed, and tensions rise when he treats a patient with a perpetual erection.
Corday clashes with new surgical resident Paul Nathan regarding his intervention into the treatment of a sickly young woman, Alison, who has signed a "do not resuscitate" order. Abby wonders about the erratic behavior of her visiting brother Eric, and feels conflicted over a nurse's official complaint against Kovac, Abby's former lover. Meanwhile, Pratt comforts Chen after a patient threatens her, and Corday suspects that an unconscious, 14-year-old female patient has been sexually assaulted.
Abby fears the worst when her brother Eric suddenly disappears. He is actually AWOL and she forges Carter's name to obtain his medical records. Carter and Chen treat a frightened Chinese immigrant nanny, Tong-Yi, whom they suspect was impregnated by her employer. Meanwhile, new surgical resident Paul Nathan, who is struggling to overcome a physical disability, tries to help in the emergency roombut his fellow doctors do not appreciate his advice to patients. Unable to quench his sexual appetites, Kovac also gets into trouble in his professional life, despite his admirable resolve to find an eye specialist to treat a young gunshot victim. Gallant and fellow medical student Erin Harkins engage in an escalating competition of medical knowledge. And Weaver gets some much-needed good news.
Abby's family nightmare continues as she and her mother Maggie search for Abby's missing brother Eric, who Abby suspects is suffering from serious mental problems. The two women go to a Midwestern air force base, hoping to prevent Eric from being court-martialed for being absent without leave. Carter struggles to get out of Chicago to join Abby. Meanwhile, Corday treats a family of patients who, while building a snowman, were severely injured after being struck by a truck driver. She must help the father, Stuart, make a life-or-death decision. Corday also sympathizes with troubled surgical resident Paul Nathan as he struggles with the increasing symptoms of his physical handicap.
Abby is distressed when her mother interferes with Eric's treatment at a psychiatric hospital. Pratt treats a frightened young girl who has been injured in an auto accident and desperately wants to hide a secret. An unhappy Luka forms an unlikely bond with a lonely elderly woman who makes him a surprising offer. Chen is overcome with upsetting memories when a baby is abandoned in the emergency room. Pratt takes action after Leon is fired from his menial job.
The past 24 hours play in reverse after Luka gets into a car accident with Erin. Luka was forced into working hungover after a staff Christmas party, leading to a patient being brain dead. At the party, he confesses to Abby that he misses her before an oblivious Carter interrupts.
Kovac faces an M&M in the aftermath of Rick Kendrick's case, with Lewis and Abby in support. When Pratt is witnessed bringing a gun into the emergency room, Carter feels compelled to defend him. However, Pratt's erratic behavior makes Carter reconsider. Weaver hopes to keep her pregnancy a secret, but physical complications might compromise her plans. Lewis warily watches self-destructive patient Chip Mealy, who admits to molesting young boys. Romano warns guilt-stricken Kovac not to admit to a grieving mother that his miscalculation caused her son's vegetative state. Chen treats a high school student who overdosed on Ritalin. And Gallant confronts the scheming young wife of an aged, dying man.
Weaver confronts a dilemma when influential alderman John Bright, seeking treatment after a fall, tests positive for syphilispotentially damaging information that could become public. Meanwhile, Carter is impressed by irascible old Doctor McNulty, who oversees an inner-city medical clinic. A sympathetic Kovac defies conventional ethics when he tricks a seriously injured patient who refuses to leave his dying wife's side into believing that she has already expired. Pratt unilaterally allows a drug-addled man to be with his terminal mother. Pratt also keeps a wary eye on his mentally challenged brother Leon as he starts a new job. And Weaver and Kovac differ on what to do with a young boy whose medical history suggests repeated child abuse.
Pratt is overwhelmed when Leon persuades him to treat a badly wounded robber who duped Leon into participating in a crime. Carter decides to take a vacation. Meanwhile, he continues to treat Dr. McNulty, who may not actually be a doctor. Emotionally fragile Romano receives negative news regarding his recovery. Kovac's relationship with Weaver deteriorates, culminating in a threat from Luka. Alderman Bright returns, bearing financial gifts of gratitude for Weaver. And a bold doctor, "Fast" Eddie Dorset, startles Corday by asking her on a date. Abby finds out for the first time that Carter is considering going to Africa with Luka for awhile.
After taking care of a wounded prostitute and bringing her case to the attention of social services, Chen confronts her past by telling Pratt about giving up her baby for adoption. Romano is furious after Anspaugh notifies him he's not allowed to take part in surgeries. Kerry is promoted in favor of Romano, due to Alderman Bright's aid. Susan has a blind date. And while Carter is out of town, Abby receives word that Eric's private plane is missing and she refuses to contact Maggie.
With Eric still missing, Maggie returns to town. Carter tells Abby he wants to marry her. Weaver gives Luka an ultimatum regarding his job. Chen tells Pratt about her son. Sean Simmons returns with pneumonia. Pratt pronounces a derelict dead when with the paramedics, who later is discovered alive by Gallant in the morgue. Weaver has her purse snatched on the street, later the same guy appears in the ER as a patient.
Three people are cuddled at Doc Magoo's. One person is severely injured. In a search for the suspects, Gallant and Pratt are pulled over and arrested while returning from the gym. They take the arrest personally, and they later confront the officers when they are brought to the ER for a different accident. Carter wants to pop the question to Abby, but decides it's not the right time. Carter gives Maggie a ride to the bus station to return to Minneapolis. Kovac is forced by Weaver to see another doctor about his attitude. Lewis spends time with Sean, as his time winds down.
Alderman Bright returns to blackmail Weaver into treating his gay lover for syphilis (off the record, of course). Unfortunately, the man dies from an allergic reaction to penicillin and Kerry is forced to cover up her mistake. Things between Abby and Carter have cooled down following Carter's aborted marriage proposal, but they soon heat up again. Luka has a very unconventional therapy session. Romano's condition forces Anspaugh to replace him as chief of staff...with Weaver.
After being pushed out of his job as Chief of Staff by Kerry, Romano takes control of the ER and wreaks havoc and manages to get himself beaten up in a bar after work. Luka tries to convince Kerry to put him on the case of a Croatian child desperately in need of heart surgery, to no avail. A young woman with terminal cancer must make a choice between life-prolonging chemotherapy and the life of her unborn child. Pratt buys a birthday gift for Chen from a street vendor whose foot was run over by Elizabeth's nanny; Susan's husband (who she married the same week she met him) unexpectedly shows up from Las Vegas.
Abby treats a psychotic patient who has overdosed on his medication. Eric, Abby's brother, finally calls. Dr. Gordana Horvat, who attended medical school with Kovac, brings a boy from Croatia who needs heart surgery. Gallant and Pratt receive their match letters. Carter receives bad news about his grandmother. Romano discusses grave options about his arm with Corday.
Kovac defies the rules to get a dying Croatian boy to Chicago in a race to save his life. Despite receiving tragic news, Carter tries to prevent grieving gang member Curtis from seeking vengeance. Carter's sad family gathering is interrupted by Abby's mentally troubled brother Eric, who has left his voluntary care facility. Meanwhile, Lewis has trouble ending her relationship with Chuck. Perez, a baseball player with a serious heart ailment, is treated on the eve of his pitching debut with the Chicago Cubs. And a tormented Romano makes a dramatic decision about his mangled arm, after it catches fire in his kitchen. Luka departs for the Congo after saying goodbye to Abby.
Carter's day shift and Pratt's night shift (his final shift at County) are intercut. Both men have extremely busy days. Doc Magoo's burns down. Luka calls Carter from the Congo and asks for help. Carter decides to go. Pratt decides to stay at County. In other parts of the hospital, Romano has his now-useless left arm amputated.
Season Finale: Carter travels to the Congo to join Luka, and quickly discovers how different things are to what he left behind. When an overdue Luka returns briefly from a remote clinic, we learn he's having a cozy relationship with French-Canadian nurse Gillian. Carter, Gillian and two aids join Luka at the clinic in order to set up an immunization program. They soon find themselves caught between the Mai-Mai and the Congolese army with several patients, among them an injured young girl and her mother. When the group must evacuate the clinic, Luka refuses to leave his patients and remains behind. Carter returns to Chicago, going to a sleeping Abby's bedside.