Abstract Subclinical endometritis (SCE) is an important postpartum disease in dairy cows but conventional cytobrush diagnosis often gives imprecise results. The aim of this study was to analyze disease-associated changes in peripheral blood as potential diagnostic parameters. Cellular subpopulations of blood leukocytes from cows with or without SCE (45 to 55 days post partum) were flow cytometrically quantified. Gene expression of whole blood leukocytes was assessed by PAXgene analysis. SCE cows showed significantly higher numbers of blood mononuclear cells (MNC) and neutrophils. Among MNC, numbers of B-cells, NK-cells and CD172a-positive monocytes were significantly elevated. Compared to non-SCE cows, blood leukocytes of SCE cows significantly expressed higher copy numbers of CXCL8, TNF and IL12. In order to test whether circulating plasma factors are responsible for these changes, leukocytes, polymorphonuclear cells (PMN) and monocyte subpopulations (classical, intermediate, non-classical) of healthy cows were stimulated with plasma of SCE and non-SCE cows. Whereas gene expression of whole leukocytes and PMN remained unaltered, plasma from SCE animals significantly elevated expressed mRNA copy numbers of CXCL8, CXCL1 and IL1B in intermediate monocytes. In conclusion, elevated numbers of selected mononuclear subpopulations in peripheral blood and enhanced expression of distinct genes encoding for inflammatory mediators in blood leukocytes reflect the subclinical uterine inflammatory process in cows. Whether the observed changes in the periphery of SCE cows are the consequence of the uterine inflammatory process, or whether they affect the pathogenesis of the disease is currently unknown.