Sibutramine, a serotonin-noradrenaline reuptake inhibitor (SNRI), has been shown to be a safe and effective weight-loss drug. The purpose of the present study was to examine whether sibutramine has an effect on macronutrient selection in both female and male rats in addition to total food intake. Wistar rats of both sexes were divided into three groups, and each group was offered a different set of three sensorily contrasting macronutrient-specific diets, each set including carbohydrate-, protein-, and fat-rich diets. Sibutramine (10 mg/kg) was shown to consistently decrease carbohydrate and fat intake at all data points regardless of gender and diet. Intake of carbohydrate differed between male and female rats at 2 h post administration with 2.5 and 5 mg/kg of sibutramine. The effect of sibutramine on protein intake was diet- and gender-specific. All doses of sibutramine decreased total food intake regardless of gender and diet group beginning at 6 h post administration. In conclusion, sibutramine affected macronutrient selection and emphasis on dietary recommendations, as well as appropriate dosage according to gender should be considered during therapy.