Some diseases and environmental exposures, including those that are risk factors for atherosclerosis, are associated with increased oxidant stress. The objective of this cross-sectional, observational study was to determine whether oxidant stress is increased during human immunodeficiency virus type 1 (HIV-1) infection or its therapy. To quantify oxidant stress, plasma F2 isoprostane (F2-IsoP) concentrations were determined by gas chromatography/mass spectroscopy. A total of 120 subjects were enrolled during routine primary care visits. The median CD4+ T cell count was 341 cells/mm3, the median HIV-1 RNA level was 3.4 log10 copies/mL, and 74% of patients were receiving antiretroviral therapy. Plasma F2-IsoP concentrations were 12-149 pg/mL (median, 31 pg/mL). In univariate analysis, higher F2-IsoP concentrations were associated with lower log10 plasma HIV-1 RNA levels (P=.009) and with efavirenz use (P=.02). Both factors remained associated with plasma F2-IsoP concentrations in multivariate analysis. Oxidant stress associated with therapeutic control of viral replication may have important implications for long-term complications of antiretroviral therapy.