CD93, also known as complement component C1q receptor, is expressed on the surface of different cellular types such as monocytes, neutrophils, platelets, microglia, and endothelial cells, and it plays a pivotal role in cell proliferation, cell migration, and formation of capillary-like structures. These processes are strictly regulated, and many fetal and maternal players are involved during placental development. At present, there are no studies in literature regarding CD93 in placental development, so we investigated CD93 expression in first and third trimester and PE placentas by immunohistochemistry and western blotting analysis. In addition, we performed in vitro experiments under oxidative stress conditions to demonstrate how oxidative stress acts on CD93 protein expression. Our data showed that CD93 was expressed in villous cytotrophoblast cells, in some fetal vessels of first and third trimester and PE placentas and in the extravillous cytotrophoblast of cell columns in the first trimester placentas. Moreover, we detected a significant decrease of CD93 expression in third trimester and PE placentas compared to first trimester placentas, while no differences were detected between third and PE placentas. No differences of CD93 expression were detected in oxidative stress conditions. We suggest that CD93 can guide extravillous cytotrophoblast migration through β1-integrin in uterine spiral arteries during placentation in the first trimester of pregnancy and that the decrease of CD93 expression in third trimester and PE placentas could be linked to the poor extravillous cytotrophoblast cells migration. So, it might be interesting to understand the role of CD93 in the first phases of PE onset.