The protagonist of My Sister’s Keeper is 13-year-old Andromeda “Anna” Fitzgerald, the youngest of three children. Her 16-year-old sister Kate has battled acute promyelocytic leukemia (APL) since the age of two. Shortly after Kate’s diagnosis, Anna’s parents Sara and Brian decided to conceive a child via in vitro fertilization who could serve as a donor for Kate. This child turned out to be Anna, who, by the time the novel begins, has donated cord blood, bone marrow, and lymphocytes to Kate. Anna and Kate are quite close, but Anna struggles with feeling as though she only exists to save Kate.
At age 16, Kate is in remission from her leukemia, but she is suffering from kidney failure due to the strain of over a decade of treatment. As a result, Sara, a stay-at-home mother who has been fiercely devoted to Kate’s treatment since her diagnosis, expects that Anna will donate a kidney in order to save Kate’s life, even though Kate’s oncologist Dr. Chance has informed the Fitzgeralds that there is a high chance of Kate dying during the transplant, which would leave Anna with one less kidney for nothing. Brian, a firefighter, is more ambivalent about having Anna donate a kidney, but he does not make his protests known. The Fitzgeralds’ son, Jesse, often acts out and is generally isolated from the family, though he still lives at the family house.
Tired of being a constant donor for Kate, Anna decides to sue her parents for medical emancipation. Without telling her parents, she seeks out Campbell Alexander, a well-known and haughty attorney who keeps a service dog but refuses to tell anyone the dog’s purpose. Campbell initially rejects Anna due to her young age, but when she tells him the details of her case, he is intrigued and decides to take her on pro bono. However, when Sara is served papers for the lawsuit in Kate’s hospital room and grows irate, Anna begins to second-guess her decision to file the lawsuit. Her wishy-washy attitude frustrates Campbell, who doubts her commitment to the case and fears that he will not be able to prove her right to autonomy if she cannot stick by her own decisions.
Judge DeSalvo, who lost his 12-year-old daughter to a drunk driver a few years earlier, is assigned to the case. Sara is a former lawyer who is still accredited by the bar, so she chooses to represent herself. The first time all the parties meet, Anna becomes distraught due to pressure from Sara to retract her lawsuit and cannot make up her mind about what to do. Unsure about Anna’s intentions, Judge DeSalvo appoints her a guardian ad litem to help guide Anna in her decision-making and make a recommendation to the court about what would be best for Anna. This guardian ad litem ends up being Julia Romano, Campbell’s ex-girlfriend that he abruptly dumped in high school. This leads to tension between the two of them, particularly since Julia suspects that Campbell has only taken Anna’s case for the publicity, since Sara and Brian have been publicly scrutinized for conceiving a “designer baby.”
Shortly after Anna’s lawsuit commences, Kate becomes extremely ill and has to be hospitalized, further straining tension in the Fitzgerald household. Jesse, unbeknownst to his firefighter father, has been setting fires around town. Meanwhile, Sara increases her pressure on Anna to drop her lawsuit. Brian decides to allow Anna to stay at the fire station with him so that she can have time to process her feelings without Sara’s pressure, which causes Sara to feel betrayed by Brian. During this time, Julia gets to know Anna better, although she also has trouble ascertaining Anna’s true motivations for filing the lawsuit. Campbell speaks to Brian, who tells him that he would be willing to testify on Anna’s behalf at the hearing.
Shortly before the hearing begins, Campbell and Julia go out to talk about the case and end up sleeping together, but Campbell leaves before Julia wakes, making her feel abandoned once again. At the hearing, both Campbell and Sara call a variety of witnesses who present various arguments both for and against Anna’s emancipation. Campbell feels confident that he will win the case since he has one of Anna’s parents as a witness, but when Brian takes the stand, he cannot in good conscience testify in favor of a decision that would result in Kate’s death and breaks down on the stand. Campbell tells Anna that she’ll have to testify instead, but Anna staunchly refuses, causing the two to get into a major argument.
Judge DeSalvo calls Julia to the stand to make her recommendation on Anna’s behalf, but for the first time in Julia’s career, she is unable to make a conclusive recommendation due to the ethical complexity of the Fitzgeralds’ situation. This spurs Anna to take the stand, where she confesses that Kate, ready to die, asked Anna to file her lawsuit in order to get out of donating her kidney. As Anna testifies, Campbell has a seizure, forcing Judge DeSalvo to call for a recess in order for him to recuperate. During the recess, Campbell confesses to Julia that he developed epilepsy after receiving a concussion and broke up with her because he thought she deserved better. Julia rejects this and vows to stay by his side. Campbell also confesses to Anna, who speculates that Campbell took her case because he knows what it’s like to lose control over his own body.
Judge DeSalvo speaks privately with Kate and declares that court will reconvene the next morning. That night, Sara and Brian spend time with Kate, coming to terms with the fact that she’ll soon die. In court, Judge DeSalvo declares his ruling: he will grant Anna her medical emancipation. His reasoning is that, since the situation is so complicated and there is no correct decision, it makes sense to leave the decision up to whether Anna wants to donate her kidney or not. Anna is deeply conflicted over the verdict, but both Sara and Brian reassure her that they’re all right with the outcome.
Sara and Brian head home ahead of Anna since she has legal paperwork to fill out, so Campbell drives Anna home afterwards. It is raining heavily, and during the drive, Campbell is T-boned by a large truck. Brian, the firefighter on duty, shows up and realizes Anna has been grievously injured. At the hospital, the doctor informs him that Anna is braindead. Campbell, who was granted medical power of attorney for Anna, signs off on her organs being donated so that Kate can receive Anna’s kidney. After Anna’s organs are extracted, Sara and Brian turn off her life support, and she dies.
In the epilogue, Kate is in her 20s, having survived the kidney transplant and remaining in remission from her leukemia despite her prognosis. After Anna’s death, the entire Fitzgerald household was thrown into intense grief, but the family eventually began to recover. Brian struggled with alcoholism but eventually recovered, and Jesse became a police officer. Kate herself became a ballet instructor and carries Anna with her wherever she goes.
