Abstract Objective Quercetin, a commonly occurring flavonoid and well known antioxidant, has been suggested to possess other beneficial activities. The present study investigated the possible anti-inflammatory effects of physiologically attainable quercetin concentrations. Methods The effects of quercetin were tested in vitro, i.e., added to blood in the test tube, and ex vivo and in vivo, i.e., in blood taken after 4 wk of administration of quercetin in an intervention study. Results Quercetin dose-dependently inhibited in vitro lipopolysaccharide-induced tumor necrosis factor-α production in the blood of healthy volunteers. At a concentration of 1 μM, quercetin caused a 23% reduction. The in vitro lipopolysaccharide-induced interleukin-10 production remained unaffected by quercetin. A 4-wk quercetin intervention resulted in a significant increase in plasma quercetin concentration. The supplementation also increased total plasma antioxidant status but did not affect glutathione, vitamin C, and uric acid plasma concentrations. Basal and ex vivo lipopolysaccharide-induced tumor necrosis factor-α levels were not altered by the intervention. Conclusion The present study shows that quercetin increases antioxidant capacity in vivo and displays anti-inflammatory effects in vitro, but not in vivo or ex vivo, in the blood of healthy volunteers. This lack of effect is probably due to their low cytokine and high antioxidant levels at baseline, indicating that neither inflammation nor oxidative stress is present. Only in people with increased levels of inflammation and oxidative stress, e.g., patients with a disease of which the pathology is associated with these two processes, might antioxidant supplementation be fruitful.