Android fat is a surrogate measure of visceral obesity in the truncal region. Both visceral adiposity and oxidative stress (OS) are linked to cardiometabolic risk factors and clinical cardiovascular disease. However, whether body fat distribution (android vs gynoid) is associated with OS remains unknown. We hypothesized that increased android fat will be associated with greater OS. Body fat distribution and markers of OS, including plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulfide) aminothiols, were estimated in 711 volunteers (67% female, 23% black, mean age 48 ± 11) enrolled in the Emory Georgia Tech Predictive Health study. At 1 year, 498 subjects had repeat testing. At baseline, anthropometric and fat distribution indexes, including body mass index, waist circumference, weight/hip ratio, and android and gynoid fat mass correlated with lower plasma concentrations of glutathione and higher cystine levels indicative of higher OS. At 1 year, the change in android but not gynoid fat mass or body mass index negatively correlated with the change in the plasma glutathione level after adjustment for cardiovascular risk factors. Increased body fat, specifically android fat mass, is an independent determinant of systemic OS, and its change is associated with a simultaneous change in OS, measured as plasma glutathione. In conclusion, our findings suggest that excess android or visceral fat contributes to the development of cardiovascular disease through modulating OS.