Changes in the blood cells’ epigenome, such as variations in DNA methylation, have been proposed as markers of the long-term effects of various factors in humans and in livestock. Therefore, this study aimed to identify pan-genomic DNA methylation variations in association with the well-being of animals submitted to contrasted welfare states. Pregnant sows of mixed parities (low parity (LP) – 2nd and 3rd gestation and high parity (HP) – 4th gestation or higher) were housed in two contrasting conditions throughout gestation (0 to 105 days): in a conventional system on a slatted floor (C: LP, n=9 and HP, n=6) or in an enriched system on accumulated straw with additional space per sow (E: LP, n=6 and HP, n=7). At gestation day 98, pan-genomic DNA methylation from the sows’ blood mononuclear cells was analysed by reduced representation bisulphite sequencing (RRBS), following the lab’s protocol. Only CpGs sites covered by at least 10 uniquely mapped reads (CpG10) were retained and filtered out using a list of 105,171 known Single Nucleotide Polymorphisms (SNPs). Methylation percentages at each CpG10 were calculated and cluster analyses were conducted. Differentially methylated cytosines (DMCs) were identified using methylKit v1.0. (Δmeth≥25% and adjusted P-value <1%) considering the following comparisons: [LPvsHP]C and [LPvsHP]E (parity effect); [CvsE]LP and [CvsE]HP (system effect). Cluster analyses revealed a clear separation corresponding to parity groups. [LPvsHP] displayed more DMC in C (5,391) than in E (3,886) with a similar loss of methylation (53 and 55% in C and E, respectively). Regarding the housing effect, the contrast [CvsE] displayed more DMCs in HP (2,769) than in LP sows (2,183), with an equal number of hypo and hyper DMCs. DMC-targeted genes were mostly associated with cell migration and adhesion, and other immune processes. Taken together, these results suggest that parity has a stronger effect on the immune cells’ methylome than the housing system.