Background: Cardiovascular diseases, cardiovascular risk factors, and mortality due to these situations are more frequently encountered in schizophrenic patients when compared with the general population. The mean platelet volume (MPV) is a surrogate biomarker of the platelet activity and an useful prognostic test in cardiometabolic diseases. The aim of this study was to investigate what influenced MPV levels in patients with schizophrenia. Materials and Methods: We evaluated hospital records of 60 hospitalized schizophrenia patients. Thirty age-and sex-matched healthy control subjects were also included as a control group. Results: MPV levels were significantly higher in patients who were on atypical antipsychotic drugs than in patients who were not using any drug (9.2 +/- 0.8 vs. 8.6 +/- 0.8 fL, P = 0.016) and also higher than control group (9.2 +/- 0.8 vs. 8.1 +/- 0.9 fL, P < 0.001). Furthermore, patients who were not using antipsychotics had higher MPV than control group (8.6 +/- 0.8 vs. 8.1 +/- 0.9 fL, P = 0.036). Atypical antipsychotic use [Odds ratio (OR) = 6.152, 95% confidence interval (CI,) P = 0.003)] and platelet distribution width (OR = 0.989, 95% CI, P = 0.032) were associated with high MPV levels in univariate analysis. In multivariate logistic regression model, only atypical antipsychotics use (OR = 6.152, 95% CI, P = 0.003) was found to be independent predictor of high MPV levels after adjustment of other potential confounders (age, gender, presence of hypertension, diabetes mellitus, hyperlipidemia, and smoking). Conclusion: MPV seems to be influenced not only by schizophrenia itself but also by atypical antipsychotic drugs. It might be concluded that schizophrenic patients are under increased risk for cardiometabolic diseases and risk factors and this risk is higher in patients on atypical antipsychotic treatment.