The events in the novel are based on Garner's spending a period caring for her friend Jenya Osborne when Osborne was dying. The narrator Helen lives next door to her daughter Eva and Eva's children, as Garner does with her daughter Alice Garner and her children, and plays the ukulele as Garner does. The novel draws heavily on both events and details from Garner's life.

Nicola only truly embraces her death when a Buddhist friend tells her that in dying, she has something to teach them. A number of friends and family, including Helen, take turns as her caretaker. The novel flashes forward to the months ahead, where Nicola returns to Sydney and eventually dies. At the end of the novel, Nicola returns to mainstream oncology treatment, and the doctors find that some of her symptoms are due to cancer having destroyed part of her vertebrae. As the three weeks of the novel progress Helen becomes increasingly angry with Nicola for denying the seriousness of her illness, forcing those around her to do emotional work on her behalf in confronting her death, and in making light of them for doing so. Helen is suspicious of the treatment and becomes more so as she sees its deleterious health effects. The cancer is considered terminal by her doctors. A friend Nicola, who is ill with bowel cancer, comes to stay with Helen in order to pursue alternative therapy for her disease. The novel is told from the first person perspective of a woman, Helen, who lives in Melbourne near her family. The Spare Room is a 2008 novel by Australian writer Helen Garner, set over the course of three weeks while the narrator, Helen, cares for a friend dying of bowel cancer.

The spare room by helen garner