The effect of meal composition and energy content on the thermic effect of food (TEF) was investigated in sixteen adult, non–obese female subjects. Each subject consumed four different test meals, each meal on a different day. Meals were of high-carbohydrate-low-fat (HCLF) with 0.70, 0.19 and o.11 of the energy content from carbohydrate, fat and protein respectively, and low-carbohydrate-high–fat (LCHF) with 0.24, 0.65 and 0.11 of the energy content from carbohydrate, fat and protein respectively. The energy contents of the test meals for each composition were 2520 kJ (600 kcal) and 5040 kJ (1200 kcal). The basal metabolic rate (BMR) and the postprandial metabolic rate (PP-MR) were measured by open-circuit indirect calorimetry using the Douglas bag technique while the subjects were in the supine position. The mean BMR value was 3.63 (SE 0.07) kJ/min (0.87 kcal/min (SE 0.17)). The 5 H-TEF value for the 2520 kJ (600 kcal) HCLF meal was 228 (SE 11.8) kJ (54 kcal (SE 2.8)) and for the LCHF meal was 228 (SE 9.6) kJ (54 kcal (SE 2.3)). The corresponding values for the 5040 kJ (1200 kcal) meals were 356 (SE 20.4) kJ (85 kcal (SE 4.9)) and 340 (SE 15.8) kJ (81 kcal (SE 3.8)). There was no significant (P =0.49) effect of meal composition on TEF, but the energy content of the meals had a significant (P < 0.001) effect on TEF. In all subjects and for all meals, PP-MR had not returned to premeal level 5 h after a meal, indicating that the TEF values measured underestimate total TFF. The present study suggests that TEF is significantly influenced by the energy content of a meal but not by meal composition.