Background Oxidant stress contributes to the pathogenesis of multiple conditions and can be assessed by measuring plasma F₂-isoprostane concentrations. We hypothesized that oxidant stress is associated with plasma homocysteine concentration and risk factors for atherosclerosis in HIV-infected women. Methods We measured plasma F₂-isoprostane concentrations in a cross-sectional study of 249 HIV-infected women attending the Bronx (NY, USA) site of the Women's Interagency HIV Study and assessed associations with plasma homocysteine concentration and other metabolic parameters by linear regression. Results In multivariate analysis, hepatitis C virus (HCV) viraemia, waist circumference, homocysteine concentration and serum aspartate aminotransferase level were positively associated with log F₂-isoprostane concentration (all P<0.005). There was a trend for an inverse association between log F₂-isoprostane and CD4⁺ T-cell percentage ( P=0.06). Among women with HCV infection, the FIB-4 index, an indirect marker of liver fibrosis derived from routine laboratory tests, was positively associated with log F₂-isoprostane concentration. Conclusions In this cross-sectional study of HIV-infected women, plasma F₂-isoprostane concentration was positively associated with homocysteine concentration, as well as HCV infection, abdominal obesity and aspartate aminotransferase level.