Abstract Background Chronic inflammation, which can be modulated by diet, is linked to high white blood cell counts and correlates with higher cardiometabolic risk and risk of more severe infections, as in the case of COVID-19. Methods Here, we assessed the association between white blood cell profile (lymphocytes, basophils, eosinophils, neutrophils, monocytes and total white blood cells) as markers of chronic inflammation, habitual diet and gut microbiome composition (determined by sequencing of the 16S RNA) in 986 healthy individuals from the PREDICT-1 nutritional intervention study. We then investigated whether the gut microbiome mediates part of the benefits of vegetable intake on lymphocyte counts. Results Higher levels of white blood cells, lymphocytes and basophils were all significantly correlated with lower habitual intake of vegetables, with vegetable intake explaining between 3.59 and 6.58% of variation in white blood cells after adjusting for covariates and multiple testing using false discovery rate (q