Skeletal muscle dysfunction is a well-recognised hallmark of COPD, leading to exercise intolerance. The vastus lateralis of these patients is characterised by reduced mitochondrial enzyme activity, whereas this is not the case in the tibialis anterior. It is however unclear if the comprised oxidative capacity in the vastus is due to reduced mitochondrial volume density.Therefore, muscle biopsies were obtained from the vastus lateralis of 6 COPD patients and 4 healthy age-matched controls and from the tibialis anterior of another 6 patients and 6 controls. Mitochondrial number, fractional area and morphometry, as well as Z-line width (as a surrogate marker of fibre type), were analysed using transmission electron microscopy.Mitochondrial number (0.34 vs. 0.63 microm(-2)) and fractional area (1.95% vs. 4.25%) were reduced in the vastus of COPD patients compared to controls, respectively. Despite a reduced mitochondrial number (0.65 vs. 0.88 microm(-2)), mitochondrial fractional area was maintained in the tibialis.It can be concluded that reduced mitochondrial fractional area is likely contribute to the decreased oxidative capacity in the vastus of COPD patients, whereas the maintained mitochondrial fractional area in the tibialis may explain the normal oxidative capacity.