Energy intake restriction causes a yo-yo effect by decreasing energy expenditure (EE) and decreasing fullness. We investigated the 24-h effect of protein and capsaicin, singly or combined, on fullness and EE during 20% energy intake restriction. The 24 participants (12 male, 12 female; BMI, 25.2 +/- 0.4 kg/m(2); age, 27 +/- 4 y; body fat, 25.6 +/- 5.7%; 3-factor eating questionnaire, F1: 6 +/- 2, F2: 4 +/- 2, F3: 3 +/- 2) underwent eight 36-h sessions in a respiration chamber. The study had a randomized crossover design with 8 randomly sequenced conditions. The participants were fed 100 or 80% of their daily energy requirements. There were 2 control (C) conditions: 100%C and 80%C; 2 conditions with capsaicin (Caps): 100%Caps and 80%Caps; 2 conditions with elevated protein (P): 100%P and 80%P; and 2 conditions with a mixture of protein and capsaicin (PCaps): 100%PCaps and 80%PCaps. Appetite profile, EE, and substrate oxidation were monitored. Compared with 100%C, the 80%C group had expected negative energy-balance effects with respect to total EE, diet-induced thermogenesis, and fullness, whereas the 80%Caps diet counteracted these effects, and the 80%P and 80%PCaps diets exceeded these effects (P < 0.01). In energy balance and negative energy balance, fat balance was more negative in the 80%Caps, P, and PCaps groups than in the 80%C group (P < 0.05) and respiratory quotient values were lower. A negative protein balance was prevented with the 80%P and 80%PCaps diets compared with the 80%C diet. Our results suggest that protein and capsaicin, consumed singly or mixed, counteracted the energy intake restriction effects on fullness and EE. During energy restriction, protein and capsaicin promoted a negative fat balance and protein treatments also prevented a negative protein balance.