Dynamic hyperinflation and leg muscle fatigue are independently associated with exercise limitation in patients with chronic obstructive pulmonary disease (COPD). The aims of the present study were to examine 1) the relationship between these limitations and 2) the effect of delaying ventilatory limitation on exercise tolerance and leg muscle fatigue.In total, 11 patients with COPD (with a forced expiratory volume in one second of 52% predicted) completed two cycling bouts breathing either room air or heliox, and one bout breathing heliox but stopping at room air isotime. End-expiratory lung volume (EELV), leg muscle fatigue and exercise time were measured.On room air, end-exercise EELV was negatively correlated with leg fatigue. Heliox increased exercise time (from 346 to 530 s) and leg fatigue (by 15%). At isotime, there was no change in leg fatigue, despite a reduction in EELV compared with end-exercise, in both room air and heliox. The change in exercise time with heliox was best correlated with room air leg fatigue and endinspiratory lung volume.Patients with chronic obstructive pulmonary disease who had greater levels of dynamic hyperinflation on room air had less muscle fatigue. These patients were more likely to increase exercise tolerance with heliox, which resulted in greater leg muscle fatigue.