The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O-2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O-2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O-2 saturation, leg arterial-venous O-2 difference, and leg O-2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 +/- 100 vs. 1,798 +/- 128 ml/min, 6 W: 1,832 +/- 109 vs. 1,992 +/- 120 ml/min, and 9W: 2,035 +/- 114 vs. 2,187 +/- 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O-2 consumption (3 W: 173 +/- 12 vs. 210 +/- 15 ml O-2/min, 6 W: 217 +/- 14 vs. 237 +/- 15 ml O-2/min, and 9 W: 244 +/- 16 vs 260 +/- 18 ml O-2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O-2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O-2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population.