Huntington's disease (HD) is caused by an abnormally expanded CAG repeat in the IT‐15 gene, which encodes a widely expressed protein called huntingtin. Abnormalities of mitochondrial respiratory chain function, specifically complex II/III, have been identified in HD striatum and defects of energy metabolism have been demonstrated in vivo in skeletal muscle in both symptomatic and presymptomatic HD patients. We have investigated respiratory chain function using histochemical and biochemical methods in HD skeletal muscle from 12 patients and compared these with 12 age and sex‐matched controls. The data from the HD patients were related to clinical parameters of HD including the Unified Huntington's Disease Rating Scale (UHDRS). There were positive correlations between CAG repeat years (a product of CAG repeat length and age) and both motor (P < 0.002) and cognitive (P < 0.01) scores of the UHDRS. There was no significant difference in the activities of complexes I to IV compared to age‐matched controls. However, there were significant correlations for individual HD complex II/III activities with disease duration (P = 0.017), repeat years (P = 0.032), and cognitive scores (P = 0.019). There was also evidence from ultrastructural studies that inclusion formation may occur in HD muscle. These results provide additional evidence that mutant huntingtin influences mitochondrial complex II/III function in non‐neuronal tissue (skeletal muscle) and suggest that muscle may be a potential marker of disease progression in HD. © 2007 Movement Disorder Society