Epigenetic modifications such as DNA methylation play a role in regulating gene expression and consequently in biological processes, such as those involved in health and disease. In human, studies provide evidences that the methylome in peripheral blood mononuclear cells (PBMC) can reflect some disease susceptibility. In dairy cows, the post calving period is characterized by profound changes associated with an immunosuppression increasing the susceptibility to diseases. This study aims to quantify the global DNA methylation levels (dMe) by LUminometric Methylation Assay in bovine PBMC and in milk leukocytes and epithelial cells. Parity, milk production and quality, health and diet were reported from 52 Holstein housed at INRA’s experimental dairy farms. Genomic DNAs were extracted from 94 PBMC samples collected at D15 and D60 of lactation. PBMC-dMe varied from 72 to 86%. The proportion of different blood cell types were determined by cytometry and were found stable during the lactation period analyzed. dMe variations do not correlate with blood cell populations. No effect of lactation period, parity or breeding was observed. Moreover, dMe of PBMC was not significantly altered in pathological cows (mastitis or uterine post-partum disease, n=6) in comparison with healthy cows (n=18). For the 24 cows at the two lactation stages, milk leukocytes (ML) and epithelial cells (MEC) were also purified after milk centrifugation and immunomagnetic binding and gDNA extracted. Using the paired samples (PBMC-ML-MEC), dMe was found to be cell type specific: 77.08±1.8% in PBMC vs 65.6±4.1% in ML (significantly different, P<0.001) and 67.39±7.9% in MEC. Further studies are needed to identify the specific changes in DNA methylation using genome-wide analysis. CIFRE fellowship from Pilardière & Codelia.