Quercetin, a flavonoid found in fruits and vegetables, is an antioxidant with anti‐inflammatory, antimicrobial, and immune‐modulating properties. The purpose of this study was to investigate the effects of quercetin supplementation on innate immune function and inflammation in humans. Female subjects (N=120, ages 30–79 y) were randomized to one of three groups, with supplements administered for 12 wk using double‐blinded procedures: Q‐500 (500 mg/d quercetin, N=38), Q‐1000 (1000 mg/d quercetin, N=40), or placebo (N=42). Fasting blood samples were obtained pre‐ and post‐study and were analyzed for plasma quercetin, IL‐6, TNF‐α, and leukocyte subsets. Natural killer cell activity (NKCA) and lymphocyte subsets were assessed on 74 subjects. Granulocyte oxidative burst activity (GOBA) and phagocytosis were assessed on 64 subjects. Quercetin supplementation at two doses compared to placebo increased plasma quercetin (P<0.001) but had no significant influence on leukocyte subsets, IL‐6, TNF‐α, NKCA, GOBA, or phagocytosis. In summary, results from this double‐blinded, placebo‐controlled, randomized trial indicated that quercetin supplementation at 500 and 1000 mg/d for 12 wk increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in healthy adult females. This work was supported by grants from Coca‐Cola and Quercegen Pharma.