INTRODUCTION: Studies have demonstrated that noninvasive ventilation improves exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). The role of heated humidified high-flow nasal cannula (HFNC) therapy in patients with COPD on self-paced exercise performance remains unclear. Therefore, the purpose of the present study was to determine whether HFNC-aided supplemental oxygen during a 6-minute walk test (6MWT) would change self-paced exercise performance and cardiopulmonary outcomes in patients with stable COPD. METHODS: A single-site, cross-over trial was conducted in a pulmonary rehabilitation outpatient department. This study enrolled 30 stable COPD patients without disability. The participants with and without HFNC performed 6MWTs on 2 consecutive days. Outcomes were the distance walked in the 6MWT, physiological, and cardiopulmonary parameters. RESULTS: Those performing HFNC-aided walking exhibited a longer walking distance than those performing unaided walking. The mean difference in meters walked between the HFNC-aided and unaided walking scenarios was 27.3 ± 35.6 m (95% CI: 14.4-40.5 m). The energy expenditure index was significantly lower when walking was aided by HHHNFC rather than unaided (median: 1.21 beats/m walked vs median: 1.37 beats/m walked, P < .001). However, there were no differences in transcutaneous carbon dioxide tension between HHHNFC and non-HHHNFC patients. CONCLUSION: Walking distance and arterial oxygen saturation improved in stable COPD patients receiving HFNC with additional oxygen support. However, HFNC did not affect transcutaneous carbon dioxide tension and the self-reported dyspnea score during the walking test. The present study demonstrated the feasibility and safety of using HFNC in self-paced exercise. TRIAL REGISTRATION: NCT03863821.