The aims of this study were to investigate whether the impairment in endurance of limb muscles is a general finding in chronic obstructive pulmonary disease (COPD) patients, affecting even those with mild-to-moderate disease or relatively normal physical activity. In addition, this study aimed to determine the physiopathology of exhaustion in local endurance tests and whether the reduction in quadriceps endurance can be predicted from muscle strength measurements. A total of 75 volunteers were assigned to one of two groups according to pulmonary function tests: COPD patients or healthy age-matched controls. Functional assessment included both quadriceps strength (maximum voluntary contraction (QMVC)), and quadriceps endurance (contractions against a load equivalent to 10% QMVC until task failure or for up to a limiting time of 30 min (QTlim)). COPD patients showed a decrease of approximately 43%, in QMVC and approximately 77% in QTlim compared with controls. Task failure occurred only in COPD patients and was due to muscle fatigue, since limiting symptoms were associated with a decrease in the median frequency of quadriceps electromyographical signal and a reversible decrease in QMVC. The impairment in skeletal muscle endurance was present even in patients with mild-to-moderate airflow obstruction and individuals with relatively normal physical activity, and was irrespective of lung function variables, anthropometrical data or quadriceps strength. Peripheral muscle endurance was impaired in chronic obstructive pulmonary disease patients, even in those with relatively normal physical activity and mild-to-moderate airflow obstruction. This impairment associated with an early onset of muscle fatigue and could not be predicted from the severity of the disease or the reduction in quadriceps strength.