In a cross-sectional study involving subjects from the Reaching for Excellence in Adolescent Health cohort, we examined the associations between HIV status, disease severity, immune activation, and oxidative damage. Subjects (265 HIV-positive and 127 HIV-negative) were young (range: 14-23 years of age) and primarily female (75%) and black (67%). Many subjects, particularly female subjects, were overweight or obese. Relatively few HIV-positive subjects had advanced HIV disease (13%), and 54% were taking antiretroviral therapy (ART). The 2 markers of oxidative damage used in this study (plasma malondialdehyde and protein carbonyl concentrations) did not correlate with each other, and neither was higher in HIV-positive subjects than in HIV-negative controls. Increased oxidative damage was seen in association with male gender, cigarette smoking, marijuana use, immune activation (as indicated by activated CD8+ T-cell counts and plasma C-reactive protein concentration), and use of ART, however. Plasma ceruloplasmin was associated with decreased oxidative damage in HIV-positive subjects, although this association was not seen in those taking ART.