Comparative effect of oyster mushrooms on plasma, fecal lipid profiles, liver and kidney functions were evaluated in hyper and normocholesterolemic rats. The feeding of hypercholesterolemic rats with 5% powder of fruiting bodies of oyster mushrooms i.e., Pleurotus ostreatus, P. sajor-caju and P. florida reduced the plasma total cholesterol level by 37%, 21% and 16%, respectively and triglyceride level by 45%, 24% and 14%, respectively. LDL/HDL ratio decreased by 64%, 45% and 41% for P. sajor-caju, P. ostreatus and P. florida fed rats, respectively. Mushroom feeding also reduced body weight in hypercholesterolemic rats. However, it had no adverse effect on plasma bilirubin, creatinin and urea nitrogen level. Mushroom feeding also increased the total lipid and cholesterol excretion through the feces. The present study reveals that feeding of 5% oyster mushroom powder do not have detrimental effects on the liver and kidneys rather may provide health benefits for the cardiovascular-related complication by decreasing the atherogenic lipid profiles.