Background: Oxidative stress during HIV infection may impair immune function, cause more rapid disease progression, and increase requirements for dietary antioxidants such as vitamins C and E. Objectives: The study had 2 principal objectives. The first was to ascertain whether HIV infection and immune activation were associated with lower plasma concentrations of ascorbate, urate, and α- and γ-tocopherols and with total antioxidant status (TAS). The second objective was to ascertain whether these antioxidants were associated with protection against oxidative damage. Design: This was a cross-sectional study involving 241 HIV-positive and 115 HIV-negative subjects aged 14-23 y. Subjects were primarily female (76%) and African American (70%), and 21% were Hispanic. Results: Plasma ascorbate was significantly lower, but γ-tocopherol and TAS were significantly higher in subjects with HIV infection when the analysis was adjusted for dietary intake and sex. Plasma α-tocopherol did not differ significantly by HIV status. Plasma γ-tocopherol also was higher in subjects with oxidative damage than in those without such damage. More than 90% of subjects had adequate plasma concentrations for both ascorbate and α-tocopherol, although α-tocopherol concentrations were lower than expected on the basis of third National Health and Nutrition Examination Survey data. Conclusions: Low plasma ascorbate concentrations in HIV-positive subjects suggest that vitamin C requirements are significantly higher in those with HIV infection. Plasma tocopherol concentrations were not depressed by HIV infection and may be maintained by compensatory mechanisms such as the activity of α-tocopherol transfer protein. © 2006 American Society for Nutrition.