CD1d is an atypical MHC class I protein that associates with a wide variety of cellular lipids. Previous work on the function of CD1d largely focused on its role in the activation of lipid-reactive Natural Killer T-cells (NKT). However, CD1d broadly associates with cellular lipids and shows abundant expression in parenchymal and bone marrow-derived cells. This raises the question of whether CD1d, in addition to its function in the activation of NKT cells, can also exert direct effects on cellular lipid metabolism in a manner independent of NKT cells. To address this question, we investigated mice deficient or proficient in CD1d that were crossed onto a genetic background deficient in Rag1, associated with loss of mature B and T cells including NKT cells. Since hepatocytes abundantly express CD1d and have major roles in lipid metabolism, we explored CD1d-dependent, NKT cell-independent functions of CD1d in the context of hepatic lipid metabolism. We show that deletion of CD1d is associated with a selective reduction in hepatocyte triglyceride and cholesterol ester content, which is independent of NKT cells. Furthermore, deletion of CD1d protects from steatosis and hepatic inflammation and damage in the context of a mouse model of diet-induced non-alcoholic fatty liver disease. Mice with hepatocyte-specific deletion of CD1d demonstrated that direct, NKT cell-independent functions of CD1d in hepatic lipid metabolism originate from cell-autonomous roles of CD1d in hepatocytes. Mechanistic studies further suggest that direct regulation of hepatocyte lipid metabolism by CD1d results from competition between CD1d and apoliprotein B (ApoB) for lipid transfer activity of the microsomal triglyceride transfer protein, an enzyme catalyzing rate-limiting steps of lipid transfer onto CD1d and ApoB. Together, these data document that, in addition to its role in the activation of NKT cells, CD1d exerts major, direct, NKT cell-independent roles in the regulation of lipid metabolism.