Excessive adipose tissue in the body may lead to adverse health effects, carbohydrate and lipid metabolism disorders, and cardiovascular diseases. The aim of this study was to analyze the effect of a standardized high-fat meal (HF) on changes in energy expenditure and changes in the oxidation of energy substrates as well as the concentration of glucose, insulin, triglycerides and homocysteine in blood serum in relation to a standardized high-carbohydrate (non-fat, HC) meal in men with different nutritional status. In this study, 26 men (aged 19–60) without carbohydrate disorders (study group GS = 13 overweight/obese; control group GC = 13 normal body weight) were examined. It was observed that following a high-fat or high-carbohydrate meal, men with excessive body weight metabolized the main nutrients differently than men with normal body weight, and postprandial insulin secretion was also different (even without any significant differences in glucose concentrations). Overweight/obesity, which is in itself a risk factor for cardiovascular disease, contributes to an increase in the concentration of other risk factors, such as the concentration of homocysteine and triglycerides, which is referred to as cardiometabolic risk. Consumption of a high-fat meal increased the number of potential risk factors for cardiovascular disease (homocysteine and triglycerides) compared to a high-carbohydrate meal.