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This study aimed to describe cardiorespiratory, quadriceps oxygenation, and muscle fatigue responses during a one-legged quadriceps isokinetic endurance exercise in chronic obstructive pulmonary disease (COPD) and control subjects.Fourteen patients with COPD and 14 control subjects performed a cardiopulmonary cycling exercise test to exhaustion to assess peak oxygen consumption (V˙O2peak), minute ventilation (V˙Epeak), and heart rate (HRpeak). They also performed a quadriceps isokinetic endurance exercise consisting in 30 maximal knee extensions at 90°·s−1 with continuous monitoring of expired gases, cardiac output, and oxygenation of the quadriceps by near-infrared spectroscopy. Total muscle work and fatigue index were also quantified.The total muscle work developed during the quadriceps isokinetic endurance exercise was 2.25 ± 0.57 kJ in COPD and 3.12 ± 0.60 kJ in controls, P < 0.001. In absolute terms, there were no between-group differences in V˙O2, V˙E, cardiac output, and HR at the end of quadriceps isokinetic endurance exercise. However, V˙E and HR reported that a fraction of their respective peak values during cardiopulmonary cycling exercise test were higher in COPD (V˙E/V˙Epeak, 69% ± 3%; HR/HRpeak, 82% ± 15%) compared with controls (V˙E/V˙Epeak, 45% ± 2%; HR/HRpeak, 71% ± 13%), all P < 0.05. During quadriceps isokinetic endurance exercise, quadriceps deoxyhemoglobin increased by 47% ± 31% in patients versus 33% ± 41% in controls (P < 0.05 from rest values) with a significant between-group differences (P = 0.025). The fatigue index during the quadriceps exercise was higher in COPD compared with controls.Although one-legged quadriceps isokinetic endurance exercise resulted in substantial central cardiorespiratory demands in COPD, this exercise was nevertheless associated with muscle overload as evidenced by muscle deoxygenation and higher muscle fatigue index in COPD compared with controls. These findings may have implications of the design of exercise training programs in COPD.