High levels of atherogenic lipids in pregnancy are associated with health complications for the mother, the fetus and the newborn. As endocrine secretory tissue, the human placenta releases apolipoproteins (apos), particularly apoA1 and apoE. However, the magnitude and the directionality of the apo secretions remain unknown. We aimed to 1) determine the amount and orientation (apical-maternal versus basal-fetal) of placentally secreted apoA1 and apoE using human perfused placenta and primary trophoblast cell (PTC) culture, 2) compare apoA1 and apoE secretions of PTC with that of hepatocytes and 3) associate the obtained results with human blood levels by determining apoA1 and apoE concentrations in maternal and fetal serum samples. In perfused placenta and serum samples, apoA1 and apoE concentrations were significantly higher at the maternal compared to the fetal side. For apoE a similar trend was found in PTC. For apoA1, the secretion to the apical side declined over time while release to the basal side was stable resulting in significantly different apoA1 concentrations between both sides. Unexpectedly, PTC secreted significantly higher amounts of apoA1 and apoE compared to hepatocytes. Our data indicate that the placenta may play an important role in maternal and fetal cholesterol homeostasis via secretion of anti-atherogenic apos.