The window of implantation of human embryos into the endometrium spans Cycle Days 20–24 of the 28-day menstrual cycle. However, uterine receptivity may not be reliably replicated in infertile patients throughout this span. Thus, it is of importance to be able to determine optimal receptivity through a minimally invasive measure. We screened expression of a number of candidate micro-RNAs (miRNAs) in endometrial tissues and serum collected from a panel of fertile women during both the proliferative phase and the secretory phase of a normal menstrual cycle. We found that several miRNAs were significantly elevated in endometrial tissues in the secretory phase versus the proliferative phase. One of these, miR-31, was found to be not only detectable in serum samples but also significantly elevated in the secretory phase versus the proliferative phase. MiR-31 is known to target several immunomodulatory factors, such as FOXP3 and CXCL12. We find that both of these factors are significantly downregulated in endometrial tissues during the secretory phase. Our data suggest that miR-31 is a potential biomarker for optimal endometrial receptivity, possibly operating through an immunosuppressive mechanism.