Rationale: Peripheral muscle alterations have been recognized to contribute to disability in COPD. Objectives and Methods: Three primary aspects of mitochondrial function were assessed in permeabilized locomotor muscle fibers from moderate-severe COPD patients to determine whether in addition to reduced muscle activity associated with disuse, specific mitochondrial alterations could underlie muscle dysfunction. Measurements and Main Results: Respiration rates per mg of fiber weight were significantly lower in COPD muscle compared to healthy age-matched controls under various respiratory states. However, when variations in mitochondrial volume were taken into account by normalizing respiration per unit of citrate synthase activity, differences between the two groups were abolished suggesting the absence of specific mitochondrial respiratory impairment in COPD. H₂O₂ production per mitochondria was higher both under basal and ADP-stimulated states suggesting that mitochondria from COPD muscle have properties that potentiate H₂O₂ release. Direct assessment of mitochondrial sensitivity to Ca²⁺ -induced opening of the permeability transition pore (PTP) indicated that mitochondria from COPD patients were more resistant to PTP opening than their counterparts in controls. Conclusions: Comparison of these results with those of recent studies comparing healthy glycolytic to oxidative muscle suggest that these differences may be attributable to a greater type II fiber expression in COPD muscle, as mitochondria within this fiber type have similar respiratory function as mitochondria from type I fibers, yet are intrinsically prone to greater release of H₂O₂ and more resistant to PTP opening. These results thus argue against the presence of pathological mitochondrial alterations in this category of COPD patients.