Patients with Parkinson's disease (PD) often lose weight, but after subthalamic nucleus deep brain stimulation (STN-DBS), they gain weight. We compared daily energy intake (DEI), resting energy expenditure (REE) and substrate oxidation rates (measured by indirect calorimetry) in nineteen STN-DBS-treated patients (Group S), thirteen others on pharmacologic treatment by levodopa (Group L) and eight control subjects. We also determined the acute effects of STN-DBS and levodopa on REE and substrate oxidation rates. STN-DBS treated patients gained 9·7 (sem 7·1) kg after surgery, whereas patients on pharmacologic treatment lost 3·8 (sem 10·0) kg since diagnosis. In STN-DBS-treated patients, REE (−16·5 %; P<0·001), lipid oxidation (−27 %; P<0·05) and protein oxidation (−46 %; P<0·05) were decreased, whereas glucose oxidation was elevated (+81 %; P<0·05) as compared to patients on pharmacologic treatment. Levodopa acutely reduced REE (−8·3 %; P<0·05) and glucose oxidation (−37 %; P<0·01) with a slight hyperglycaemic effect (after levodopa challenge: 5·6 (sem 0·8) v. before levodopa challenge: 5·3 (sem 0·6) mmol/l; P<0·01). Switching ‘on’ STN-DBS acutely reduced REE (−17·5 %; P<0·01) and lipid oxidation (−24 %; P<0·001) 30 min after starting stimulation. Fasting glycaemia was slightly but significantly reduced (5·4 (sem 1·4) v. 5·5 (sem 1·3) mmol/l; P<0·01). After STN-DBS, the normalization of REE and the reduction in lipid and protein oxidation contribute to the restoration of weight. As levodopa decreases glucose oxidation, the reduction in daily dose of levodopa in STN-DBS-treated patients helps prevent the effect of weight gain on glycaemia.