In accordance with a previous study,23 plasma inflammatory cytokine levels were unchanged by the exercise test in both groups, suggesting that local muscle exercise does not induce systemic inflammation. However, COPD patients showed an increased systemic oxidative stress response after single-leg exercise compared with control subjects, suggesting that exercise did not induce systemic inflammation to the same extent as oxidative stress. Increased urinary MDA levels were observed immediately after exercise in COPD patients, providing evidence for local exercise-induced oxidative stress in these patients. Moreover, urinary uric acid was significantly increased immediately after exercise in COPD patients compared with healthy control subjects, which could point to an increased production of free radicals due to xanthine oxidase activity. Uric acid is the end product of purine metabolism in humans and is an indicator of xanthine oxidase activity, which is seen as an important source of ROS.24,25 In healthy control subjects, the levels of the ubiquitous antioxidant GSH decreased 2 h after exercise. Previously, studies1,26 have shown that limb skeletal muscle mass of COPD patients is reduced compared with that of control subjects. Moreover, the duration of the exercise test was shorter in COPD patients. Therefore, it is feasible that less GSH is needed during exercise in comparison with healthy control subjects. Although statistical significance was not reached, GSSG and the GSSG/GSH ratio slightly increased in COPD patients after exercise, which indicates an increased oxidative stress response after localized exercise in COPD patients. This finding is in agreement with previous studies7,27 that have reported increased GSSG/GSH ratio after exhaustive whole-body exercise. These results suggest that in patients with COPD the antioxidant system is not able to cope with the higher rate of exercise-induced ROS production, thus leaving skeletal muscle more susceptible to oxidative stress. As a localized exercise minimizes cardiorespiratory responses, we suggest that the contracting muscle was, at least in part, the source of the exercise-induced systemic oxidative stress in COPD patients. However, it cannot completely rule out that the increased oxidative stress response in COPD patients originated from sources other than the quadriceps (eg, the liver or heart).