This study investigated whether the −3826 A→G nucleotide variant of the uncoupling protein-1 (UCP1) gene is correlated with postprandial thermogenesis after a high fat meal in children. Healthy boys, aged 8–11 yr, were examined for resting energy expenditure and the thermic effect of a meal (TEM), which were measured by indirect calorimetry for 180 min after a high fat (70% fat, 20% carbohydrate, and 10% protein, providing 30% of the daily energy requirement) and a high carbohydrate meal (20% fat, 70% carbohydrate, and 10% protein). The sympatho-vagal activities were assessed by means of spectral analysis of the heart rate variability during the same period. Children were genotyped for UCP1 polymorphism by applying a PCR-restriction fragment length polymorphism using buccal samples. There was no reaction of sympathetic activity to the high carbohydrate meal in eitherthe GG allele or the AA+AG group and no significant difference in TEM. However, after the high fat meal, sympathetic responses were found in both groups; further, the GG allele group showed significantly lower TEM than the AA+AG group. In conclusion, despite fat-induced sympathetic stimulation, GG allele carriers have a lowered capacity of TEM in response to fat intake, suggesting that such impaired UCP1-linked thermogenesis can have adverse effects on the regulation of body weight.