Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. Methods: Soluble HLA-G (sHLA-G) levels were measured using a BioVendor sHLA-G ELISA kit following the manufacturer’s protocol. The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. Results: Soluble HLA-G levels were higher among women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. Soluble HLA-G levels were also higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery. Conclusion: Although sHLA-G levels were higher among women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, this may be playing a role in the maintenance of maternal immune tolerance to fetal antigen, since plasma sHLA-G levels increased with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion.