Context: The symptomatic benefits of oxygen in patients with cancer who have nonhypoxic dyspnea are not well defined. Objective: To determine whether or not oxygen is more effective than air in decreasing dyspnea and fatigue and increasing distance walked during a 6-minute walk test. Patients and methods: Patients with advanced cancer who had no severe hypoxemia (i.e., had an O-2 saturation level of greater than or equal to 90\%) at rest and had a dyspnea intensity of greater than or equal to 3 on a scale of 0 - 10 (0=no shortness of breath, 10=worst imaginable shortness of breath) were recruited from an outpatient thoracic clinic at a comprehensive cancer center. This was a double-blind, randomized crossover trial. Supplemental oxygen or air ( 5 L/min) was administered via nasal cannula during a 6-minute walk test. The outcome measures were dyspnea at 3 and 6 minutes, fatigue at 6 minutes, and distance walked. We also measured oxygen saturation levels at baseline, before second treatment phase, and at the end of study. Results: In 33 evaluable patients ( 31 with lung cancer), no significant differences between treatment groups were observed in dyspnea, fatigue, or distance walked ( dyspnea at 3 minutes: P=0.61; dyspnea, fatigue, and distance walked at 6 minutes: P=0.81, 0.37, and 0.23, respectively). Conclusions: Currently, the routine use of supplemental oxygen for dyspnea during exercise in this patient population cannot be recommended.