Aim: Leptin is produced by the adipose tissue and reduces body weight by decreasing appetite and increasing metabolism. Patients treated with antipsychotics often have treatment-induced weight-gain, leading to other metabolic complications. Obese subjects often have leptin resistance, which is defined as the presence of hyperleptinemia in obesity. We evaluated leptin resistance in subjects with schizophrenia in comparison with healthy controls of similar body composition. Methods: We determined fasting serum leptin levels and body composition parameters in 30 subjects with schizophrenia and 30 healthy, age- and sex-matched controls. Both groups were of comparable amount of body fat and lean body mass. Leptin resistance was measured as the ratio between resting energy expenditure (REE, calculated using the results of body composition analysis) and the leptin level. Results: There was no difference in the level of fasting serum leptin between the patients and the control group; there were also no differences between men in the schizophrenia and in the control groups and between women in the schizophrenia and in the control groups. Women had a significantly higher level of leptin in the schizophrenia group, in the control group and in the whole study sample (p < 0.001 for all comparisons). REE was comparable between both study groups. REE was higher in men in the whole study sample and in both study groups (p < 0.001 for all comparisons). The REE:leptin ratio did not differ between both groups. As above, the REE:leptin ratio was significantly higher in men in the schizophrenia group, in the control group and in the whole study sample (p < 0.001 for all comparisons). Conclusion: We found no differences in REE, fasting serum leptin levels and leptin resistance. However, certain differences in leptin resistance between schizophrenia patients and healthy controls may play a role in weight gain induced by antipsychotics.