Oxidation of low-density lipoprotein (LDL) lipid is implicated in atherogenesis and certain antioxidants inhibit atherosclerosis. Ubiquinol-10 (CoQ 10 H 2 ) inhibits LDL lipid peroxidation in vitro although it is not known whether such activity occurs in vivo, and, if so, whether this is anti-atherogenic. We therefore tested the effect of ubiquinone-10 (CoQ 10 ) supplemented at 1% (w/w) on aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E–deficient (apoE−/−) mice fed a high-fat diet. Hydroperoxides of cholesteryl esters and triacylglycerols (together referred to as LOOH) and their corresponding alcohols were used as the marker for lipoprotein lipid oxidation. Atherosclerosis was assessed by morphometry at the aortic root, proximal and distal arch, and the descending thoracic and abdominal aorta. Compared to controls, CoQ 10 -treatment increased plasma coenzyme Q, ascorbate, and the CoQ 10 H 2 : CoQ 10 + CoQ 10 H 2 ratio, decreased plasma α-tocopherol (α-TOH), and had no effect on cholesterol and cholesterylester alcohols (CE-OH). Plasma from CoQ 10 -supplemented mice was more resistant to ex vivo lipid peroxidation. CoQ 10 treatment increased aortic coenzyme Q and α-TOH and decreased the absolute concentration of LOOH, whereas tissue cholesterol, cholesteryl esters, CE-OH, and LOOH expressed per bisallylic hydrogen-containing lipids were not significantly different. CoQ 10 -treatment significantly decreased lesion size in the aortic root and the ascending and the descending aorta. Together these data show that CoQ 10 decreases the absolute concentration of aortic LOOH and atherosclerosis in apoE−/− mice.