We hypothesized that in patients with COPD, poor nutritional status adversely influences exercise tolerance by limiting aerobic capacity of exercising muscles. In 28 patients with stable COPD, we correlated nutritional status with gas exchange indexes obtained during maximal incremental cycle ergometer exercise and with respiratory function parameters. On the basis of percent of ideal body weight (%IBW), patients were divided into three groups (GP): GP1 (n = 8, %IBW < 90); GP2 (n = 13, %IBW > or = 90 < 110); and GP3 (n = 7, %IBW > or = 110). When compared with normally nourished individuals (GPs 2 and 3), malnourished GP1 patients showed greater reduction in maximal workload and in peak O2 uptake (VO2 peak), with earlier onset of metabolic acidosis (anaerobic threshold [AT]); in addition, indexes reflecting O2 cost of ventilation were higher in GP1. Nutritional status could be correlated with exercise tolerance (VO2 peak, r = 0.82, p < 0.0001), with onset of metabolic acidosis (AT, r = 0.69, p < 0.0001) and with dead space/tidal volume ratio (VD/VT, r = -0.59, p < 0.001). Body weight was inversely correlated with indexes that are likely to reflect the increase in O2 cost of ventilation. We conclude that in patients with stable COPD, (1) malnutrition significantly affects muscle aerobic capacity and exercise tolerance, and (2) high wasted ventilation and O2 cost of ventilation may be responsible for the weight loss.