In general, high-fat (HF) diets are associated with the development of several metabolic diseases including obesity, diabetes, and cardiovascular disease. However, it is important to consider the composition of fat intake within the diet, due to the differential impact that dietary fatty acids have on physiological function. Current dietary recommendations center on reducing saturated (SFA) and trans-fatty acid intake, and increasing mono-unsaturated fatty acid (MUFA) and poly-unsaturated fatty acid (PUFA) intake. Eating fats high in MUFAs and PUFAs instead of SFA has been linked to reduced disease risk. However, less is known regarding differences in physiological function between MUFA and PUFA intake. The objective of this dissertation is to compare a HF diet rich in MUFAs to a HF diet rich in PUFAs to determine potential differences in metabolism, cholesterol levels, and appetite responses, in normal weight, healthy adults in a single-blind crossover-design. In Manuscript #1, resting substrate oxidation and diet induced thermogenesis (DIT) was measured, acutely and after 5-day HF diets. Acutely, postprandial fat oxidation was lower after a HF PUFA-rich meal compared to a HF MUFA-rich meal. However, after a 5-day HF PUFA-rich diet, there were no differences between MUFAs and PUFAs, meaning fat oxidation increased after a 5-day HF PUFA diet. In Manuscript #2, fasting lipids were measured before and after 5-day HF diets, with significantly more favorable fasting lipid values observed after the 5-day HF PUFA-rich diet. Postprandial triglycerides were also significantly lower after the 5-day HF PUFA-rich diet compared to the HF MUFA-rich diet. In Manuscript #3, appetite responses were measured acutely and after 5-day HF diets. A 5-day HF PUFA-rich diet led to lower postprandial ratings of hunger and lower concentrations of the hunger hormone ghrelin compared to a 5-day HF MUFA-rich diet. However, no significant differences in energy intake at a buffet meal were observed between diets. There were also no differences in ratings of fullness or concentrations of the satiety hormone PYY between diets. All in all, these results indicate that a HF PUFA-rich diet may have more favorable metabolic outcomes compared to a HF MUFA-rich diet in healthy, normal weight males.