Liver can function as part of the innate and adaptive immune systems. We hypothesize that prostaglandins participate in the regulation of hepatic immune function during early pregnancy in sheep. The objective of this study was to elucidate expression of prostaglandin synthase in ovine liver during early pregnancy. Ovine livers were sampled on day 16 of the estrous cycle, and days 13, 16, and 25 of pregnancy, and the expression of prostaglandin synthases, including prostaglandin-endoperoxide synthase 1 (PTGS1), PTGS2, prostaglandin E synthase (PTGES), and aldo-keto reductase family 1, member B1, a prostaglandin F synthase (PGFS), were detected by quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry analysis. There were increases in the expression of mRNA and the proteins of PTGS2, PTGES, and PGFS in the livers during early pregnancy, but PTGS1 was decreased in the pregnant ewes. The PGFS protein was limited to the hepatocytes and the endothelial cells of the proper hepatic arteries and hepatic portal veins. In summary, the upregulation of PTGS2, PTGES, and PGFS and downregulation of PTGS1 may be involved in the maternal hepatic immune adjustment during early pregnancy in sheep.