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To determine the influence of 2 wk of quercetin (Q; 1000 mg·d−1) compared with placebo (P) supplementation on exercise performance and skeletal muscle mitochondrial biogenesis in untrained, young adult males (N = 26, age = 20.2 ± 0.4 yr, V˙O2max = 46.3 ± 1.2 mL·kg−1·min−1).Using a randomized, crossover design with a 2-wk washout period, subjects provided blood and muscle biopsy samples presupplementation and postsupplementation periods and were given 12-min time trials on 15% graded treadmills after 60 min of moderate exercise preloads at 60% V˙O2max.Plasma Q levels rose significantly in Q versus P during the 2-wk supplementation period (interaction P value <0.001). During the 12-min trial, the net change in distance achieved was significantly greater during Q (2.9%) compared with P (−1.2%; 29.5 ± 11.5 vs −11.9 ± 16.0 m, respectively, P = 0.038). Skeletal muscle messenger RNA expression tended to increase (range = 16-25%) during Q versus P for sirtuin 1 (interaction effect, P = 0.152), peroxisome proliferator-activated receptor γ coactivator-1α (P = 0.192), cytochrome c oxidase (P = 0.081), and citrate synthase (P = 0.166). Muscle mitochondrial DNA (relative copy number per diploid nuclear genome) increased 140 ± 154 (4.1%) with Q compared with −225 ± 157 (6.0% decrease) with P (P = 0.098).In summary, 1000 mg·d−1 Q versus P for 2 wk by untrained males was associated with a small but significant improvement in 12-min treadmill time trial performance and modest but insignificant increases in the relative copy number of mitochondrial DNA and messenger RNA levels of four genes related to mitochondrial biogenesis.