Single snapshot measurements of resting energy expenditure (REE) suggest that hypermetabolism contributes to cancer cachexia, but tumor impact on total 24-hr energy expenditure (TEE) is unknown. Automated multicage indirect calorimetry was employed to measure daily energy expenditure in adult Buffalo rats (n = 16) randomized to tumor inoculation or controls. Measurements included baseline REE, activity EE (AEE), thermic response to food (TEF), and TEE. Rats (n = 16) were randomized. Metabolic measurements, tumor size, and body weight were recorded weekly. Animals were sacrificed at Week 5 for analysis of host and tumor composition. Significant depletion of total lean body mass occurred in TB rats (> 15%wt loss, ANOVA P < 0.001) which inversely correlated with tumor growth (r = −0.81, P < 0.001). REE, TEF, AEE, and TEE did not change in controls (ANOVA P = n.s.). In TB rats, a 19.5%increase in REE occurred (119.4 ± 3.3 to 138.7 ± 1.8 kcal/kg LBM/day, P < 0.01). TEE remained unchanged (157.3 ± 5.6 vs 152.9 ± 3.6 kcal/kg LBM/day, P = n.s.) due to a 66%decrease in AEE (32.9 ± 3.1 to 10.5 ± 1.7 kcal/kg LBM/day, P = 0.01). TEF did not change (4.7 ± 0.8 vs 5.0 ± 0.3 kcal/kg LBM/day, P = n.s.). Both TB and controls demonstrated a decreased REE in response to a 24-hr fast (7.9%vs 4.8%, P = n.s.). Respiratory quotient decreased in both groups when comparing fed to fasted values: TB (0.86 to 0.76) and controls (0.86 to 0.71), but the decline was greater in controls (P = 0.04). Tumor-host interaction results in an increase in REE, but continuous measurements of EE indicate that the effect upon TEE may be offset by a decrease in physical activity. During fasting, a normal adaptive decrement in REE was maintained, but conversion to a fat-burning state was impaired in TB rats compared to controls.