['Growth hormone-deficient (GHD) adults often report impaired quality of life (QoL) - with fatigue, a key element. This deficit can improve following GH replacement. The basis of this response is unclear. Perturbations in skeletal muscle metabolism have been demonstrated in several conditions in which fatigue is a prominent symptom. We wished to define the role of skeletal muscle metabolism in the impaired QoL observed in patients with GHD.', 'To compare in vivo skeletal muscle mitochondrial oxidative phosphorylation using phosphorus-31 magnetic resonance spectroscopy in matched untreated GHD adults, treated GHD adults and healthy volunteers.', 'Twenty-two untreated GHD adults, 23 treated GHD adults and 20 healthy volunteers were recruited at a regional centre. All patients underwent assessment of muscle mitochondrial function (τ₁/₂ PCr) and proton handling using spectroscopy. Fasting biochemical analyses and anthropometric measurement were obtained. All patients completed the QoL-AGHDA and physical activity assessment (IPAQ) questionnaires.', 'Untreated and treated GHD adults complained of significantly increased fatigue and an impaired QoL (P = 0·002) when compared to healthy controls. There was no difference in maximal mitochondrial function (P = 0·53) nor pH recovery (P = 0·38) of skeletal muscle between the three groups. Untreated GHD patients had significantly lower IGF-1 than both treated GHD and healthy volunteers (P < 0·001), but there was no association between τ₁/₂ PCr and serum IGF-1 (r = -0·13, P = 0·32).'] Is impaired quality of life in growth hormone-deficient adults independent of the altered skeletal muscle oxidative metabolism found in conditions with peripheral fatigue?