BACKGROUND: Mechanisms underlying weight loss maintenance after gastric bypass surgery are poorly understood. Our aim was to examine the effects of gastric bypass on energy expenditure in rats. METHODS: Thirty diet-induced obese male Wistar rats underwent either gastric bypass (n=14), sham operation ad libitum fed (n=8) or sham-operation body weight-matched (n=8). Energy expenditure was measured in an open circuit calorimetry system. RESULTS: Body weight after 70 days was lower after gastric bypass compared to sham ad libitum fed rats (p<0.0001). Sham-operated body weight-matched controls ate less than gastric bypass animals to reach the same weight (16.2+/-0.5g vs. 27.5+/-0.8g, p<0.001). Twenty-four hour energy expenditure was increased after gastric bypass (4.50+/-0.04 kcal/kg/h) compared to sham-operated ad libitum fed (4.29+/-0.08 kcal/kg/h) and sham-operated body weight-matched controls (3.98+/-0.10 kcal/kg/h, p<0.001). Gastric bypass rats showed higher energy expenditure during the light phase than both sham-operated control groups (sham ad lib: 3.63+/-0.04 kcal/kg/h vs. sham body weight-matched: 3.42+/-0.05 kcal/kg/h vs. bypass: 4.12+/-0.03 kcal/kg/h, p<0.001). Diet-induced thermogenesis was elevated after gastric bypass compared to sham-operated body weight-matched controls three hours after a test meal (0.41+/-1.9% vs. 10.5+/-2.0%, p<0.05). The small bowel of gastric bypass rats was 72.1% heavier due to hypertrophy compared with sham-operated ad libitum fed rats (p<0.0001). CONCLUSIONS: Gastric bypass surgery in rats prevented the expected decrease in energy expenditure subsequent to weight loss. Diet-induced thermogenesis was higher after gastric bypass compared to body weight-matched controls. Raised energy expenditure may be an additional mechanism explaining the physiological basis of weight loss after gastric bypass surgery.