The purpose of this study was to measure and investigate the acute effects of two fatty meals (high-SFA & high-PUFA) on post-prandial thermic effect, substrate oxidation, and satiety. Eight healthy adults (four males and four females) aged 19-22 years were assigned to consume two isocaloric meals: high in saturated fatty acids from butter and high in polyunsaturated fatty acids from sesame oil. Indirect calorimetry was used to measure resting energy expenditure (REE), post-prandial energy expenditure for five hours, and substrate oxidation. Satiety of the subjects after meals was estimated by using visual analogue scales (VAS). Five hours thermic effect of food (TEF) was not significantly different between butter meal (6.5% of energy intake) and sesame oil meal (7.3% of energy intake), but, the TEF of butter meal reached the peak point at 150 min and decreased more rapidly arriving to REE in 270 min. On the other hand, TEF of sesame oil meal reached the peak at 90 min and decreased slower than butter meal (still higher than REE at 300 min). No significant differences in substrate oxidation rates were found between the two meals. Post-prandial fat oxidation rates increased significantly after the consumption of both butter and sesame oil meal than that of the pre-prandial state. Satiety values (hunger, fullness, and appetite) were similar among the meals, but recovery of hunger and fullness to the pre-prandial state was faster in butter meal than that of the sesame oil meal.