BACKGROUND: Exercise desaturation in patients with COPD is a pathophysiological phenomenon that is not wholly understood and whose clinical consequences are still unclear. METHODS: Eighty-three patients with moderate to severe COPD and P Sp02 > 60 mm Hg who desaturated during the 6-min walk test were followed for 5 years. Forty-eight patients had early desaturation (S Sp02 fell below 90% less than one minute after starting the walk test). Spirometry, blood-gas measurements, and 6-min walk tests were performed every 6 months. We recorded 6-min walk distance, baseline S Sp02 , lowest S Sp02 , and the time to S Sp02 < 90%. In each control, stable patients with severe hypoxia at rest who required long-term oxygen therapy were identified. RESULTS: Upon completion of the study, 65% of the early desaturators had developed severe hypoxemia and required long-term home oxygen, versus 11% in the non-early desaturators (P < .001). CONCLUSIONS: In patients with moderate to severe COPD, desaturation within the first minute of the 6-min walk test predicts the need for long-term home oxygen at 5-year follow-up.