Compensatory changes in energy intake (EI) and macronutrient metabolism in response to modest covert underfeeding were tested by whole-body calorimetry in eight lean men. Each was studied on three occasions comprising a controlled stabilization day followed by manipulation and outcome days in a whole-body calorimeter. On the manipulation day EI was fixed, and calculated to maintain energy balance (CONTROL) or to provide 85% of CONTROL by removing energy as carbohydrate (CHOred) or as fat (FATred). On the outcome day, ad libitum EI was allowed at fixed mealtimes. CHOred and FATred manipulations generated significantly different energy balances (-1.10 (SE 0.13) MJ, P=0.000; -1.10 (SE 0.12) MJ, P=0.000) and fat balances (-0.61(SE 0.23) MJ, P=0.03; -1.09 (SE 0.20) MJ, P=0.000), but not carbohydrate balances (-0.39 (SE 0.22) MJ, NS; 0.11 (SE 0.23) MJ, NS) by the end of the manipulation day compared with CONTROL. On the outcome day, EI was significantly higher than CONTROL after CHOred (+1.58 (SE 0.33) MJ, P=0.004) and FATred (+1.21 (SE 0.49) MJ, P=0.022) with no differences between treatments. Overall 48 h energy balances averaged close to zero at -0.14, +0.34, +0.04 MJ on CONTROL, CHOred and FATred respectively. Total 48 h energy intakes on CHOred and FATred averaged 101 (SE 1.7)% and 99 (SE 2.5)% of CONTROL, thus demonstrating accurate detection of a mild energy deficit and efficient next-day compensation. Despite significant differences in macronutrient oxidation rates, the energy homeostatic mechanism appeared to be independent of specific macronutrient deficits.