The effects of supplemental oxygen (O2) versus air on working calf muscle metabolism were studied in seven patients with stable chronic obstructive pulmonary disease (COPD) and chronic hypoxemia (PaO2 = 57 +/- 3 SE mm Hg) and seven age-matched control subjects. Oxygen and air were randomly administrated at 24-h intervals, and O2 flow rate was adjusted to correct hypoxemia (PaO2 = 87 +/- 4 mm Hg) in the COPD group. The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined with 31P magnetic resonance spectroscopy at rest, during a graded standardized and localized exercise protocol (360 active plantar flexions), and during recovery. In resting muscle no significant effect of added O2 was demonstrable in each group with regard to pHi, Pi/PCr, and ATP/(PCr+Pi+PME) ratios. Mechanical data were similar between the two groups and between the two tests during the whole exercise. The indices of muscular oxidative metabolism (Pi/PCr and pHi at the end of exercise and recovering PCr resynthesis rate) were impaired in the COPD group compared with that in the control group during air (all p < 0.05). All these parameters were significantly improved with added O2 in the COPD group (p < 0.05), whereas no similar effects were observed in the control group. However, these beneficial effects were incomplete since the exercising Pi/PCr ratio remained higher in the COPD group than in the control group during added O2. This energetic muscular impairment could correspond to tissular damage related to chronic hypoxemia.