Sibutramine is a serotonin-noradrenaline reuptake inhibitor (SNRI) which has been shown to be a safe and effective weight-loss drug. The purpose of this 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 diets, each set included a carbohydrate-rich diet, a protein-rich diet and a fat-rich diet. Sibutramine (10mg/kg) was shown to consistently decrease carbohydrate and fat intake at all data points regardless of gender and diets. 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 should be considered during therapy.