The Lost Weekend is a tragic work detailing the alcoholic madness of Don Birnam, a New Yorker who lives with his brother Wick. The story begins with Don alone in the accommodation he shares with his brother, the latter having gone out to a concert with their mutual friend and Don’s former lover Helen. Though Don has made it three days without touching alcohol, he gives in to temptation steals the money Wick had meant to pay a cleaner. He heads out to a local bar, Sam’s, where he stares at himself in a mirror. While doing this, he thinks up a short story called “In The Glass,” in which he would tell the story of how alcohol has ruined his youth and young manhood. Returning to his apartment, he sees his brother leaving on a weekend away, which had originally been meant as a time for Don to get away from alcohol, but which he has now ruined with his relapse. He sits and regrets the times he has betrayed his brother, the brother who is now providing him with personal and financial support.

He cheers up once he has had another drink and heads out to a bar, where he pretends to be sophisticated and classy. He doesn’t feel so classy, however, when, having attempted to steal a woman’s handbag, he is caught by the bouncers and has to rush home in shame. When he wakes up next, he has no conception of the time of day and feels only self-disgust at his fantasies the previous night. He also rejects the idea he had for a short story, afraid that no one will bother reading it. Now aware of his situation, how he can never stop drinking and yet also that drinking leads only to more suffering, he decides to drink at home, which he believes is a safer environment. However, he gets to fantasizing again, imagining himself as a musician, and this gets him so restless that he heads back to Sam’s, the very same bar he was expelled from the previous night. He convinces Gloria, a bartender, to go on a date with him by saying that he is wealthy.

On returning home, Don’s thoughts again drift into melancholia, as he recalls his being kicked out of a fraternity while at college for the crime of being gay. The next morning, his need for alcohol is such that he decides to sell his typewriter. After finding that every establishment where he might achieve this is closed, he borrows money from a shopkeeper and pays for more alcohol. While drinking in his apartment, the realization hits him that, though his efforts to sell his typewriter might function as a short story, he has no friends left who might read it because of his drinking. He goes out to get more drinking done but falls down a flight of steps and slams his head on the pavement.

Waking up in hospital he is treated by an emotionless, detached sort of doctor and a rather aggressive male nurse, who seems to be attempting to seduce him or perhaps to mock him. Don is keen to get more drinking done, and so he signs himself out of the hospital and swaps his watch for alcohol while at Sam’s. He apologizes to Gloria for not attending the date he had made with her, saying that he doesn’t remember having made it at all. The fantasies resume when he is back in his flat, and for a time he is happy, imagining himself as a professor of literature and as an actor....