Aim: The use of psychotropic medications has been correlated with increases in body weight, body fat and waist circumference and related impairments in glucose and lipid metabolism. Hence, individuals with serious mental illness present an increased risk for obesity, metabolic complications and chronic diseases compared to the general population. Significant gender differences have been reported in the pattern and symptoms of mental illnesses, despite no differences in the overall prevalence of mental disorders between genders. However, there is a paucity of research on the effect of gender on the obesity prevalence and metabolic profile of individuals with serious mental illness. The purpose of this study was to examine the effect of gender on weight gain during psychotropic medication treatment and its effects on the metabolic profile of individuals with serious mental illness. Methods: 360 individuals with serious mental illness (Males n=89, Females n=271, age: 41.30±12.07 years, BMI: 33.88±6.64 kg/m2) volunteered to participate in the study. Measurements of body height and weight, waist circumference, body composition and basic metabolic rate were performed. Biochemical tests for blood glucose and lipid profile were conducted. Results: Men exhibited a significantly greater body weight gain during the psychotropic medication treatment (Men:23.60±15.02 vs Women:17.96±12.80 Kgs, P<0.05) despite no significant gender differences in the years of treatment (Men:66.86±64.79, Women:62.37±72.29 months, P>0.05 ). Men also had a significantly greater body weight, body mass index (BMI), percent body fat and waist circumference compared to females. In terms of metabolic profile, men exhibited greater levels of blood glucose and triglycerides and lower levels of high density lipoprotein cholesterol compared to females (P<0.05). Significant correlations were found between duration of treatment and weight gain, percent body fat and waist circumference (P<0.01). Conclusions: Men with serious mental illness appear to gain significantly more body weight during treatment with psychotropic medication compared to women, despite the similar duration of treatment. Men also exhibit a more severe metabolic profile, possibly placing them at a greater risk for chronic diseases compared to females. Hence, it is possible that the treatment for serious mental illness needs to be tailored to the gender of the individuals in order to minimize greater risks for obesity and related co-morbidities.