Studies on sex differences among adults with human immunodeficiency virus (HIV) have shown conflicting results. We sought to evaluate sex differences in morbidity and mortality among perinatally HIV-infected children. The study population included HIV-infected children born in 1990-1998 and enrolled in the Centers for Disease Control and Prevention (Atlanta, Ga)–funded the Pediatric Spectrum of HIV Disease project in 10 hospitals in New York City, NY. Medical records were reviewed every 6 months or until the child was no longer in care at the sites or died. All study children, stratified into 3 birth cohorts (1990-1992, 1993-1995, and 1996-1998), were evaluated for HIV infection within 3 months of birth.