Dante Remus Lăzărescu (Ioan Fiscuteanu), a cranky retired engineer, lives alone as a widower with his three cats in a Bucharest apartment. In the grip of extreme pain, Lăzărescu calls for an ambulance, but when none arrives, he asks for his neighbors' help. Not having the medicine Lăzărescu wants, the neighbors give him some pills for his nausea. A neighbor reveals that Lăzărescu is a heavy drinker. His neighbor helps Lăzărescu back to his apartment and to bed. They call again for an ambulance.

When the ambulance finally arrives, the nurse, Mioara (Luminița Gheorghiu), dispels the idea that Lăzărescu's ulcer surgery over a decade before could cause this pain. While taking the patient history, she suspects that Lăzărescu has colon cancer. After informing his sister, who lives in a different city, that the condition could be serious and she should visit Lăzărescu in the hospital, the nurse decides to get him to a hospital. His sister makes arrangements to come the following day; his only child, a daughter, lives in Toronto, Canada.

The film follows Lăzărescu's journey through the night, as he is carried from one hospital to the next. At the first three hospitals, the doctors, after much delay, reluctantly agree to examine Lăzărescu. Then, although finding that he is gravely ill and needs emergency surgery, each team refuses to admit him and sends him to another hospital. Meanwhile, Lăzărescu's condition deteriorates rapidly, his speech is reduced to babbling, and he slowly loses consciousness. The hospitals are jammed with injured passengers from a bus accident, but some doctors appear to reject him out of fatigue or because they do not feel like taking care of a smelly old drunkard. During the night, his only advocate is Mioara, the paramedic who stubbornly stays by him and tries to get him hospitalized and treated, while passively accepting verbal abuse from the doctors who look down on her.

Finally, at the fourth hospital, the doctors admit Lăzărescu. The film ends as they prepare to perform an emergency operation to remove a blood clot in his brain.