BACKGROUND Acute energy deficits imposed by food restriction increase appetite and energy intake; however, these outcomes remain unchanged when energy deficits are imposed by exercise. OBJECTIVE Our objective was to determine the potential role of acylated ghrelin and peptide YY(3-36) (PYY(3-36)) in mediating appetite and energy intake responses to identical energy deficits imposed by food restriction and exercise. METHODS Twelve healthy males completed three 9-h trials (exercise deficit, food deficit, and control) in a randomized counterbalanced design. Participants ran for 90 min (70% of VO(2) max) at the beginning of the exercise deficit trial and then rested for 7.5 h. Participants remained sedentary throughout the food deficit and control trials. Test meals were consumed by participants at 2 and 4.75 h in all trials. The amount provided in the food deficit trial was restricted so that an energy deficit (equivalent to that imposed by exercise) was induced relative to control. Participants were permitted access to a buffet meal at 8 h. RESULTS The energy deficits imposed by food restriction (4820 ± 151 kJ) and exercise (4715 ± 113 kJ) were similar. Appetite and ad libitum energy intake responded in a compensatory fashion to food restriction yet were not influenced by exercise. Plasma acylated ghrelin concentrations increased, whereas PYY(3-36) decreased, in response to food restriction (two-way ANOVA, trial × time interaction, P < 0.001 for each). Exercise did not induce such compensatory responses. CONCLUSIONS These findings suggest a mediating role of acylated ghrelin and PYY(3-36) in determining divergent feeding responses to energy deficits imposed by food restriction and exercise.