ABSTRACT: Oxidative stress may contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). This study sought to determine the effect of an acute oral antioxidant cocktail (AOC, vitamins C and E, and alpha-lipoic acid) on skeletal muscle function during dynamic quadriceps exercise in COPD.Ten patients with COPD performed knee extensor exercise to exhaustion and isotime trials after either the AOC or placebo (PL). Pre- to postexercise changes in quadriceps maximal voluntary contractions and potentiated twitch forces (Q(tw,pot)) quantified quadriceps fatigue.Under PL conditions, the plasma electron paramagnetic resonance (EPR) spectroscopy signal was inversely correlated with the forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC), an index of lung dysfunction (r = -0.61, P = 0.02), and maximal voluntary contraction force (r = -0.56, P = 0.04). AOC consumption increased plasma ascorbate levels (10.1 ± 2.2 to 24.1 ± 3.8 ?g · mL(-1), P < 0.05) and attenuated the area under the curve of the EPR spectroscopy free radical signal (11.6 ± 3.7 to 4.8 ± 2.2 AU, P < 0.05), but it did not alter the endurance time or quadriceps fatigue. The ability of the AOC to decrease the EPR spectroscopy signal, however, was prominent in those with high basal free radicals (n = 5, PL, 19.7 ± 5.8, to AOC, 5.8 ± 4.5 AU; P < 0.05) with minimal effects in those with low levels (n = 5, PL, 1.6 ± 0.5, to AOC, 3.4 ± 1.1 AU).These data document a relation between directly measured free radicals and lung dysfunction and the ability of the AOC to decrease oxidative stress in COPD. Acute amelioration of free radicals, however, does not appear to affect dynamic quadriceps exercise performance.