Platelet (PLT) and white blood cell (WBC) counts are 2 markers of inflammation and have been linked to the risk for cerebrovascular and coronary heart disease. A Mediterranean diet (MD) has been associated with reduced inflammation and mortality for major chronic diseases. We aimed at evaluating the association between the MD and both PLT and WBC counts. This cross-sectional analysis in a population-based cohort study included 14,586 healthy Italian citizens enrolled within the Moli-sani study. Adherence to MD was appraised by either the MD Score (MDS) or the Italian Mediterranean Index (IMI). PLT and WBC counts were both inversely related to MD adherence (MDS: P < .0001 and P = .008, respectively). As compared with those with poorer MD adherence, subjects with greater adherence had both reduced odds of being in the highest PLT-count group (MDS: odds ratio = 0.50; 95% confidence interval, 0.31-0.80) and increased odds of being in the lowest WBC-count group (IMI: odds ratio = 1.41; 95% confidence interval, 1.07-1.86). The association between WBC count and MDS disappeared when further adjusted for PLT count, whereas the association between PLT count and the MD was not affected by adjustment for WBCs. Food antioxidant and dietary fiber content modified the inverse association between MDS and WBC count and partially accounted for the association with PLTs.