The amount and composition of food eaten influence body weight regulation, which requires that, in the long term, energy intake matches energy expenditure and that the oxidation rate to be equal to intake for each and separate nutrients. The aim of this study was to examine the influence of two liquid formulas with different macronutrient composition, a high carbohydrate (HC) meal as compared to a high fat (HF) meal, on substrate oxidation and on thermic effect of food (TEF). Eighteen lean and healthy women which were fed a HC diet during the 3 preceding d were studied for a further 4 h after meal intake. The test meals provided fixed energy intake and whose calculated FQ were 0.77 for HF meal, and 0.96 for HC meal. The mean NPRQs were higher (P < 0.01) in the HC group than in the HF group, even with values greater than 1.00 indicating net lipid synthesis (NL), and which correlated with metabolic rate (MR) value (P < 0.05), glucose (P < 0.05), and heart rate (HR) values. Carbohydrate (CHO) oxidation was higher with the HC than with HF meal (P < 0.01) and correlated with the MR (P < 0.05). Protein oxidation rate rose above baseline (P < 0.01); this increase was accompanied by with a negative CHO balance. It is concluded that the change in fuel selection and the increase of TEF is mainly due to CHO intake and metabolism, respectively, and that surplus of dietary CHO of preceding days together with a large load of CHO can exceed the glycogen storage capacity and trigger NL.