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Introduction: Recurrent pregnancy loss (RPL) is defined as three or more miscarriages prior to the 20th week of gestation. This condition occurs in 15-20% of all pregnancies. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) protein that is expressed on the trophoblast cells. The purpose of this study was to evaluate the presence of anti-GRP78 antibodies in the sera of women with RPL.   Materials & Methods: This case-control study was conducted 80 women referring to the Infertility Center of Shiraz University of Medical Sciences, Shiraz, Iran, during 2014-2016. The study population was assigned into two groups of case entailing 38 women with unexplained RPL and control including 42 healthy pregnant women with no history of miscarriage and a minimum of two successful pregnancies. The measurement of the anti-GRP78 antibody in the sera of the two groups was performed using the enzyme-linked immunosorbent assay (ELISA). Furthermore, western blot technique was used to assess the expression of GRP78 in placenta tissue for both groups.   Findings: The results of the western blot demonstrated the expression of GRP78 on the trophoblast cells in both groups. Furthermore, anti-GRP78 antibodies were detected in both case and control groups through ELISA. The case group had a lower level of anti-GRP78 antibodies; however, this difference was not statistically significant (P=0.1).   Discussion & Conclusions: The findings of the current study revealed no significant difference [Zamen1] between anti-GRP78 antibody level in RPL patients and healthy pregnant subjects.