OBJECTIVE To quantify the effects of acute oxygen supplementation on lower limb blood flow (QLEG), O2 delivery (QO2LEG), and O2 uptake (VO2LEG) during exercise and to determine whether the metabolic capacity of the lower limb is exhausted at peak exercise during room air breathing in patients with COPD. METHODS Oxygen (FIO2 = 0.75) and air were randomly administered to 14 patients with COPD (FEV1: 35 +/- 2% pred, mean +/- SEM) during two symptom-limited incremental cycle exercise tests. Before exercise, a cannula was installed in a radial artery and a thermodilution catheter inserted in the right femoral vein. At each exercise step, five-breath averages of respiratory rate, tidal volume, and ventilation (VE), dyspnea and leg fatigue scores, arterial and venous blood gases, and QLEG were obtained. From these measurements, VO2LEG was calculated. RESULTS Peak exercise capacity increased from 46 +/- 3 W in room air to 59 +/- 5 W when supplemental oxygen was used (P < 0.001). QLEG, QO2LEG, and VO2LEG were greater at peak exercise with O2 than with air (P < 0.05). During submaximal exercise, dyspnea score and VE were significantly reduced with O2 (P < 0.05), whereas QLEG, VO2LEG, and leg fatigue were similar under both experimental conditions. The improvement in peak exercise work rate correlated with the increase in peak QO2LEG (r = 0.66, P < 0.01), peak VO2LEG (r = 0.53, P < 0.05), and reduction in dyspnea at iso-exercise intensity (r = 0.56, P < 0.05). CONCLUSIONS The improvement in peak exercise capacity with oxygen supplementation could be explained by the reduction in dyspnea at submaximal exercise and the increases in QO2LEG and VO2LEG, which enabled the exercising muscles to perform more external work. These data indicate that the metabolic capacity of the lower limb muscles was not exhausted at peak exercise during room air breathing in these patients with COPD.