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Clozapine is thought to have the highest risk of cardiometabolic side effects among antipsychotic medications and characteristically associated with weight gain. Despite the clozapine’s tendency to cause weight gain; we reported a patient with substantial weight loss after commencing treatment with clozapine. The patient is a 27-year-old male with a 7-years history of schizophrenia. Over the previous years he had received a number of first and second-generation antipsychotic medications with a partial improvement of symptoms but no remission of his illness. After commencement of clozapine treatment, he experienced a significant weight loss of about 20kg within a period of 6-7 months. There is no evidence to explain the weight loss in physical examination and detailed investigations of the patient, who had no previous diagnosis of a metabolic disease or another medical condition. It is suggested that, clozapine-induced weight loss is often associated with neuroreceptor affinities of the drug, individual genetic variations of receptors, obsessive-compulsive symptoms (compulsive exercise and dieting or obsessionality with food) that may occur because of clozapine and symptomatic and functional improvement provided by treatment.