PURPOSE: Recent studies suggest that, compared to healthy individuals, people with chronic obstructive pulmonary disease (pwCOPD) present a reduced capacity to perform cognitive-motor dual-task (CMDT). However, these studies were focused on short-duration CMDT offering limited insight to prolonged CMDT inducing fatigue, which can be encountered in daily life. The present study aimed to explore the effect of adding a cognitive task during repeated muscle contractions on muscle endurance, neuromuscular fatigability, and cognitive control in pwCOPD compared to healthy participants. METHODS: Thirteen pwCOPD and thirteen age- and sex-matched healthy participants performed submaximal isometric contractions of the knee extensors until exhaustion in two experimental sessions: (1) without cognitive task and (2) with a concurrent working memory task (i.e., 1-back task). Neuromuscular fatigability (as well as central and peripheral components measured by peripheral magnetic stimulation), cognitive performance, and perceived muscle fatigue were assessed throughout the fatiguing tasks. RESULTS: Independently to the experimental condition, pwCOPD exhibited lower muscle endurance compared to healthy participants (p = 0.039), mainly explained by earlier peripheral fatigue and faster attainment of higher perceived muscle fatigue (p <
0.05). However, neither effect of cognitive task (p = 0.223) nor interaction effect (group × condition
p = 0.136) was revealed for muscle endurance. Interestingly, cognitive control was significantly reduced only in pwCOPD at the end of CMDT (p <
0.015), suggesting greater difficulty for patients with dual tasking under fatigue. CONCLUSION: These findings provide novel insights into how and why fatigue develops in COPD in dual-task context, offering a rationale for including such tasks in rehabilitation programs.