BACKGROUND: Exercise is known to improve physical capacity and muscle mass in patients with chronic obstructive pulmonary disease (COPD). However, recent evidence suggests that exercise may also negatively influence metabolism in COPD. OBJECTIVE: The objective was to investigate whether exercise influences whole-body protein metabolism differently in COPD patients and control subjects and to elucidate the effect of the specific underlying lung disease. DESIGN: Whole-body protein synthesis and breakdown and urea synthesis were measured by using stable-isotope methods in 14 male patients with severe COPD (forced expiratory volume in 1 s: 37 +/- 12% of predicted) and in 8 male control subjects during and after 20 min of exercise. Subjects were normal weight [body mass index (in kg/m2) of COPD patients and control subjects: 25.8 +/- 3.9 and 25.7 +/- 4.4, respectively]. The COPD group was selected to include patients with (Emph+, n = 7) and without (Emph-, n = 7) emphysema. Absolute workload was 35 +/- 5 W, corresponding to 17 +/- 2%, 33 +/- 9%, and 52 +/- 14% of the maximal obtained workload in the control, Emph-, and Emph+ groups. RESULTS: Exercise induced a 9% increase in protein synthesis and breakdown in the Emph- and control groups, which normalized postexercise. In the Emph+ group, protein turnover did not change significantly during exercise but decreased postexercise (+/- 10%). Exercise did not change net protein breakdown (protein breakdown - synthesis) or urea synthesis, except in the Emph+ group, which showed a 14% reduction in urea synthesis postexercise (P < 0.05). CONCLUSION: Low-intensity exercise suppresses whole-body protein and urea turnover in COPD patients with emphysema and needs to be considered when maximal anabolism is targeted through a combination of exercise and nutrition.