In vitro and animal data suggest that quercetin affects adipogenesis and basal metabolism; however, whether this metabolic effect translates to reductions in body mass or improvement in body composition in humans is unknown. This study investigated 12-week supplementation of 2 different doses of quercetin, combined with vitamin C and niacin, on body mass and composition in a large, heterogeneous group of adults (n = 941; 60% female, 40% male; 18-85 years of age; 45% normal body mass index, 30% overweight, 25% obese). Subjects were randomized into 3 groups, with supplements administered in double-blind fashion: Q500 = 500 mg quercetin·day(-1), Q1000 = 1000 mg quercetin·day(-1), and placebo. Quercetin supplements were consumed twice daily over a 12-week period, and pre- and poststudy body mass and composition measurements were taken in an overnight fasted state. A general linear model was used to predict change in body mass and composition across groups with adjustment for demographic and lifestyle factors. Plasma quercetin increased in a dose-responsive manner in both Q500 and Q1000 groups relative to placebo. After adjustment for confounders, no significant differences in body mass (males interaction p value = 0.721, females p = 0.366) or body composition (males p = 0.650, females p = 0.639) were found between Q500 or Q1000 groups compared with placebo. No group differences in body mass or body composition were found in a subgroup of overweight and obese subjects. High-dose quercetin supplementation (500 and 1000 mg·day(-1)) for 12 weeks in a large, heterogeneous group of adults did not affect body mass or composition.