Postpartum dairy cows undergo significant physiological changes and require an increase in the intake of energy, proteins and minerals. When physiological processes fail to coordinate it can cause maladaptation, leading to immune dysfunction and conception failure. Prostaglandins (PGs) a major component of eicosanoids have been associated with physiological adaptation and recovery during this critical period. Recently, there has been an increased interest in exosomes and their roles in cell-cell communication. Exosomes can circulate and provide tissue-specific messages that can alter the targeted cell functions. In this study, exosomes were isolated from plasma of cows at high-risk (HR-EXO; n=20), and low-risk (LR-EXO; n=20) for metabolic and infectious diseases, and co-incubated with bovine endometrial epithelial (bEEL) and stromal (bCSC) cell lines. PGs were measured from cell culture media and eicosanoid enzyme gene expression was determined from cells after treatment. Co-incubation of bCSC with LR-EXO increased the production of PGE2 and PGF2α in comparison to basal bCSC (P= 0.02 and P= 0.03; respectively) and bCSC with HR-EXO (P= 0.03 and P= 0.04; respectively). Real-time PCR results show that when bCSC cells were co-incubated with HR-EXO, DAGLA expression was decreased (P= 0.03), but when co-incubated with LR-EXO TBXAS1 expression was increased (P= 0.01). These results suggest that LR-EXO and HR-EXO affect endometrial cells differentially and we suggest that exosomes have roles in postpartum dairy cow adaptation to transition from pregnancy to lactation.