We describe an adult woman infected with human immunodeficiency virus type 1 (HIV-1) who developed dilated cardiomyopathy (DCM) with histologically confirmed mitochondrial damage while receiving anti-HIV-1 combination therapy that included nelfinavir, lamivudine, and zidovudine. DCM resolved after discontinuation of the regimen, and cardiac function remained normal after initiation of treatment with nelfinavir, lamivudine, and abacavir, which indicates that DCM was induced by mitochondrial toxicity, most likely caused by zidovudine.