Transient re-oxygenation of humans suffering from chronic obstructive pulmonary disease (COPD) allows the assessment of the consequences of chronic hypoxemia on peripheral muscle and metabolism apart from the effects of de-conditioning. The subjects performed maximal voluntary contractions (MVC) of flexor digitorum and vastus lateralis muscles and sustained infra-maximal contractions. COPD patients repeated the whole challenge during a 50-min oxygen breathing period and after recovery to baseline hypoxemia. We measured the compound evoked muscle mass action potential (M-wave) and the medium frequency (MF) of surface electromyography (EMG) power spectrum. Blood lactate (LA) and potassium (K+), erythrocyte-reduced glutathione (GSH), and plasma thiobarbituric acid reactive substances (TBARS) were also measured. Compared with a control group, COPD patients had lower MVCs, an attenuated decrease in MF during exercise, lower resting level of GSH, no posthandgrip TBARS increase and no GSH consumption. Reoxygenation (1) increased MVCs, (2) accentuated the MF decline and (3) elicited a posthandgrip TBARS increase and GSH consumption. Thus, we conclude that chronic hypoxemia exerts specific muscular effects: a reduced force production, an attenuated 'muscle wisdom', and the suppression of the exercise oxidative stress.