Meal composition is a contributing factor to fat gain. In this study, we investigated the relationship between postprandial nutrient balance, satiety, and hormone changes induced by a high-fat meal vs. a moderate-fat meal. Ten prepubertal obese boys (BMI z-score range: 1.3-3.0) were recruited. Two meals (energy: 590 kcal) were compared: (i) high-fat (HF) meal: 12% protein, 52% fat, 36% carbohydrates; (ii) moderate-fat (MF) meal: 12% protein, 27% fat, 61% carbohydrates. Pre- and postprandial (5 h) substrate oxidation (indirect calorimetry), appetite (visual analogue scale), biochemical parameters and gastrointestinal hormone concentrations were measured. Carbohydrate balance was significantly (P < 0.001) lower (31.3 (5.7) g/5 h vs. 66.9 (5.9) g/5 h) and fat balance was significantly (P < 0.001) higher (11.5 (3.3) g/5 h vs. -0.7 (2.9) g/5 h) after HF than MF meal. Appetite (area under the curve (AUC)) was significantly reduced after an MF than an HF meal (494 (55) cm.300 min vs. 595 (57) cm.300 min, P < 0.05). Postprandial triglyceride concentration (AUC) was significantly (P < 0.05) higher after an HF than an MF meal: 141.1 (30.3) mmol.300 min/l vs. 79.3 (23.8) mmol.300 min/l, respectively. Peptide YY (PYY), cholecystokinin (CCK), and ghrelin concentrations (AUC) were not significantly different after an HF and MF meal. Glucagon-like peptide-1 (GLP-1) was significantly (P < 0.05) higher after an HF than after an MF meal (72.3 (9.8) ng/ml vs. 22.7 (7.6) ng/ml, respectively), but it did not affect subjective appetite. In conclusion, an MF meal induced a better postprandial metabolic nutrient balance, triglyceride levels, and appetite suppression than an HF meal. Gastrointestinal hormones were not related to clinically assessed hunger suppression after both meals.