A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a several-fold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP-1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we (1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, (2) estimated change in UCP-1 gene expression in BAT by RT-PRC and western blot, and (3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague Dawley rats was enforced for 20 days with the platform (flowerpot) method where muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing ~11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP-1 mRNA and immunoreactive UCP-1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP-1 in BAT.