•The influence of fatty acid composition of cow ghee, olive oil and flaxseed oil on lutein absorption was investigated in mice.•Postprandial lutein responses were in the order; cow ghee > olive oil > flaxseed oil.•The postprandial plasma lutein level with cow ghee reached the maximum (Cmax) within 2 h (Tmax).•Cow ghee elevated lutein accumulation in brain and eye by 1.34 and 1.51 folds, respectively.•Cow ghee can be exploited as an effective carrier of lutein to improve its absorption and uptake in the gut. In India, cow-ghee has been used in traditional medicinal preparations to solubilize lipophilic drugs and enhance intestinal absorption. However, reports exploring the role of cow-ghee, naturally rich in saturated fatty acids, in carotenoid chemistry is nil. We attempted to understand the influence of fatty-acid composition of cow-ghee and edible oils on intestinal absorption of lutein in mice. The postprandial plasma lutein level in the mice administered with cow-ghee significantly (p < 0.05) reached the maximum (Cmax-135.76 pmol/mL; AUC-592.80 pmol.h/mL) within 2 h (Tmax). Cow-ghee improved oral bioavailability of lutein by 2.02, 1.41 and 1.66 folds in comparison to control, olive oil and flaxseed oil respectively. Cow-ghee, composed of 69.28% saturated fatty-acids, has the potential to be a delivery vehicle for lutein as evidenced by higher postprandial triglyceride levels. This study is first of its kind which reports the influence of saturated fatty-acids on the oral bioavailability of lutein in an in-vivo system.