Purpose: Oxidant stress may be an effect of antiretroviral therapy (ART) or chronic HIV infection. Plasma F2-isoprostanes (F2-IsoP) reflect lipid peroxidation and oxidant stress and have been described in ART-associated toxicities. We explored factors associated with F 2-IsoP in HIV-infected adults. Methods: HIV-infected adults enrolled in this cross-sectional study were (a) on ART including zidovudine or stavudine but not non-nucleoside reverse transcriptase inhibitors (NNRTI), (b) on ART including NNRTI, or (c) not on ART. Plasma F2-IsoP levels were quantified by GC/MS, and clinical and laboratory data were collected at enrollment. Results: Among 285 participants, 24% were female, 37% were African American, and 194 (68%) were on ART; 44 (23%) of whom were receiving efavirenz, 45 (23%) nevirapine, and 85 (44%) protease inhibitors. Median F2-IsoP was lower in those on NNRTI than those on ART without NNRTI (p = .02). In a multivariable model, factors independently associated with increased F 2-IsoP were female sex (p = .002), higher BMI (p = .01), and heavy smoking (p = .004). There was a trend toward lower F2-IsoP among nevirapine users (p = .054). Conclusions: Among HIV-infected adults, oxidant stress status differs by sex, BMI, smoking status, and perhaps specific ART. Prospective studies should better define relationships between oxidant stress and complications of HIV infection and its therapy. © 2009 Thomas Land Publishers, Inc.