BACKGROUND : Mean platelet volume (MPV) is a measure of platelet size and activity. We conducted a population study with National Health and Nutrition Examination Survey (NHANES) data to understand the relationship of MPV with health and diseases. METHODS : The NHANES is a cross-sectional survey of non-institutionalized adult population, administered every 2 years by the Centers for Disease Control and Prevention. Participants answer a questionnaire, receive a physical examination, and undergo laboratory tests. Values of MPV were collected over 6 years (2011-2016). Logistic regression was used to predict likelihood of being in categories with MPV < 10th percentile or >90th percentile. Statistical analysis was performed using Stata/SE 15.1. RESULTS : In our study with 17,969 individuals, the mean MPV was 8.40 [SD = 0.92] femtoliter. Individuals with male sex, age 45-64 years, and recent hospital-stay were more likely to have MPV < 10th percentile. Obese, Blacks and Mexican Americans had higher odds of having MPV > 90th percentile. Individuals with emphysema had significantly higher adjusted Odds [OR 1.92, 95% CI: 1.11-3.31, p = 0.021] of MPV < 10th percentile. Individuals with cancer were less likely to have MPV > 90th percentile [OR 0.74, 95% CI: 0.55-0.99, p = 0.042]. A diagnosis of coronary artery disease, asthma, and chronic obstructive pulmonary disease did not have significant associations with MPV. CONCLUSIONS : Obese individuals are more likely to have higher MPV. Individuals with emphysema had higher odds of having MPV < 10th percentile and those with cancer were less likely to have MPV > 90th percentile.