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Background: Voluntary sleep restriction is a lifestyle feature of modern societies that may contribute to obesity and diabetes. The aim of the study was to investigate the impact of partial sleep deprivation on the regulation of energy balance and insulin sensitivity. Subjects and Methods: In a controlled intervention, 14 healthy women (age 23-38 years, BMI 20.0-36.6 kg/m(2)) were investigated after 2 nights of >8 h sleep/night (T0), after 4 nights of consecutively increasing sleep curtailment (7 h sleep/ night, 6 h sleep/night, 6 h sleep/night and 4 h sleep/night; T1) and after 2 nights of sleep recovery (>8 h sleep/night; T2). Resting and total energy expenditure (REE, TEE), glucose-induced thermogenesis (GIT), physical activity, energy intake, glucose tolerance and endocrine parameters were assessed. Results: After a decrease in sleep du-ration, energy intake (+20%), body weight (+0.4 kg), leptin / fat mass (+29%), free triiodothyronine (+19%), free thyroxine (+10%) and GIT (+34%) significantly increased (all p < 0.05). Mean REE, physical activity, TEE, oral glucose tolerance, and ghrelin levels remained unchanged at T1. The effect of sleep loss on GIT, fT3 and fT4 levels was inversely related to fat mass. Conclusion: Short-term sleep deprivation increased energy intake and led to a net weight gain in women. The effect of sleep restriction on energy expenditure needs to be specifically addressed in future studies using reference methods for total energy expenditure.