Purpose <p>Lower white blood cell, neutrophil and lymphocyte counts have been reported in vegetarians. However, studies on this topic revealed conflicting results and most observations stem from small studies using convenience sampling techniques. Additional large studies investigating associations between vegetarian diets and whole blood count (WBC) data are thus warranted.</p> Methods <p>We examined WBC and hematological parameters in US vegetarians based on complex, multistage, probability sampling design-based data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES). Crude and multivariable regression-adjusted cell counts were compared between lacto-ovo-vegetarians (LOVs), semi-vegetarians (SVGs) and omnivores.</p> Results <p>The analysis included <i>n</i> = 8232 unweighted observations, thereof <i>n</i> = 98 LOVs and <i>n</i> = 110 SVGs. Vegetarians were characterized by a younger age, a healthier BMI, and a higher proportion of females. Crude and adjusted white blood cell counts were lower in LOVs but did not differ significantly from omnivores. Except for lower red blood cell counts and hemoglobin levels in vegetarians, no significant between group differences in WBC data were found. White blood cell counts correlated significantly with the BMI and selenium intake in LOVs (<i>r</i> = 0.27 for both). Each additional µg of dietary vitamin B12 was associated with an increase in white blood cells by 0.11*1000 cells/µl in vegetarians.</p> Conclusion <p>While hemogram alterations were directionally consistent with previous studies, differences in white blood cells and neutrophils were not significant between NHANES vegetarians and omnivores. Statistical and design-specific aspects as well the elevated BMI in the vegetarian subpopulation could serve as potential explanations.</p>