Increased platelet activation and aggregation which are closely related to cardiovascular complications have been reported in patients with obstructive sleep apnea (OSA). The aim of this study was to assess the mean platelet volume (MPV), an indicator of platelet activation in patients with OSA. The 95 subjects referred for evaluation of OSA underwent overnight polysomnography. Blood samples were taken for MPV determination. According to the apnea-hypopnea index (AHI), subjects were divided into three groups; group 1: control subjects without OSA (AHI < 5, n = 24), group 2: patients with mild to moderate OSA (AHI: 5-30, n = 42), and group 3: severe OSA (AHI > 30, n = 29). Body mass index (BMI) of patients with severe OSA was significantly higher than control subjects (31.5 ± 4.0 vs. 28.2 ± 5.0; p = 0.02). The MPV was significantly higher in patients with severe OSA than in the control group (8.9 ± 1.0 vs. 8.2 ± 0.7 fl; p = 0.01). Correlation analysis within 71 patients with OSA indicated that MPV was correlated with AHI (p < 0.001, r = 0.44) and DI (p = 0.001, r = 0.37). In multivariate regression analysis, when MPV was taken as independent with other study variables which are potential confounders such as age, gender and BMI, MPV was independently correlated with both AHI (β = 0.44, p < 0.001) and DI (β = 0.38, p < 0.001). We have shown that MPV was significantly higher in patients with severe OSA when compared with control subjects and MPV was correlated with AHI and DI.