ABSTRACT: Weight loss from exercise is often less than expected. Putative compensatory mechanisms may limit exercise-induced reductions in body fat and might be proportional to exercise energy expenditure (ExEE). This study was conducted to determine compensation for (the difference between accumulated exercise energy expenditure and changes in body tissue energy stores) and compensatory responses to 1,500 or 3,000 kcal/wk of ExEE. Overweight-to-obese ( n = 36) sedentary men and women were randomized to groups expending 300 or 600 kcal/exercise session, 5 days/wk, for 12 wk. Fourteen participants in the 300-kcal group and 15 in the 600-kcal group completed the study. The primary outcome was energy compensation assessed through changes in body tissue energy stores. Secondary outcomes were putative compensatory responses of resting metabolic rate, food reinforcement, dietary intake, and serum acylated ghrelin and glucagon-like peptide-1. All measures were determined pre- and posttraining. The 3,000 kcal/wk group decreased ( P < 0.01) percentage and kilograms of body fat, while the 1,500 kcal/wk group did not. The 1,500 and 3,000 kcal/wk groups compensated for 943 (-164 to 2,050) and 1,007 (32 to 1,982) kcal/wk (mean, 95% CI, P ? 0.93), or 62.9% and 33.6% of ExEE, respectively. Resting metabolic rate and energy intake did not change. Food reinforcement and glucagon-like peptide-1 decreased ( P?< 0.02), whereas acylated ghrelin increased ( P ? 0.02). Compensation is not proportional to ExEE. Similar energy compensation occurred in response to1,500 and 3,000 kcal/wk of ExEE. ExEE of 3,000 kcal/wk is sufficient to exceed compensatory responses and reduce fat mass.