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White blood cells (WBCs) are considered a reliable biomarker of inflammation. Elevations in both WBCs and pro-inflammatory cytokines are associated with several chronic conditions. Diet is a strong moderator of inflammation and WBCs. The purpose of this study was to examine the association between the Dietary Inflammatory Index (DII®) and WBCs using data from the United States National Health and Nutrition Examination Survey (NHANES). NHANES is a cross-sectional study that occurs in two-year cycles. Respondents from five cycles (n = 26,046) with available data on diet (collected through a single 24-h dietary recall [24HR]) and WBCs (derived using the Coulter method) were included. The DII (theoretical range is about −8 to +8) was derived from the micro and macronutrients calculated from the 24HR. Linear regression models, using survey design procedures, were used to estimate adjusted mean WBC (i.e., total, lymphocytes, monocytes, and neutrophils) counts and percentages by DII quartiles. Among all participants no statistically significant difference in WBCs were observed when comparing DII quartile 4 (most pro-inflammatory) to quartile 1 (most anti-inflammatory). However, a one-unit increase in the DII was associated with a 0.028 (1000 per µL) increase in total WBCs (p = .01). Additionally, a 0.024 increase in neutrophils (p < .01) was observed for a one-unit increase in the DII. In the group of participants with normal body mass index (BMI, 18.5–24.9 kg/m 2 ), those in DII quartile 4 had higher levels of total WBCs compared to subjects with normal BMI in DII quartile 1 (7.12 vs. 6.88, p = .01). Similar comparisons were observed for monocytes and neutrophils. However, these relationships were not observed for participants who were overweight or obese, which are pro-inflammatory conditions. Normal-weight individuals consuming more pro-inflammatory diets were more likely to have elevated WBCs. Because of its cross-sectional design, NHANES cannot inform directly on temporal relations, thus limiting causal inference. Future research is needed to examine the impact of anti-inflammatory diet adoption on lowering levels of WBCs, in addition to other inflammatory mediators. [ABSTRACT FROM AUTHOR]