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Aim: Fat oxidation is impaired in obesity. The aim of the present study was to determine if fat oxidation, seen in a high-protein meal response, was influenced by body composition. Methods: Subjects were provided with control (14% protein, glycaemic index, GI 65), high-protein high-GI (33% protein, GI 74) and high-protein low-GI (35% protein, GI 45) meals. Substrate oxidation and energy expenditure were measured in room calorimeters over eight hours in 18 subjects. Results were compared using a repeated-measures anova with a customised post-hoc analysis (to compare the protein diets averaged vs control and to compare the low- and high-GI diets) and covariates in a linear model of the form: y = α + β1 × fat-free mass (kg) + β2 × loge fat mass (kg). Results: The full model found significant meal effects on fat oxidation (0.21 ± 0.21 kcal/minute high-protein high-GI, 0.34 ± 0.11 kcal/minute high-protein low-GI, 0.55 ± 0.2 kcal/minute control, F = 3.50, P = 0.007). The effect on energy expenditure (1.67 ± 0.07 kcal/minute high-protein high-GI, 1.61 ± 0.08 kcal/minute high-protein low-GI, 1.67 ± 0.08 kcal/minute control) approached significance (F = 2.45, P = 0.070). Post-hoc analysis revealed a protein effect (P = 0.004 for fat oxidation and P = 0.030 for energy expenditure). Significant interactions indicated that meal response was influenced by body composition. The high-protein meals eliminated the negative relationship between body fat and fat oxidation (α = −4.7, β2 = 2.23, P