Oxidative stress is an important trigger in the complex chain of events leading to neurodegenerative diseases. On the other hand, dietary fatty acids play an essential role in brain function. The objectives of this study were to assess the effect of dietary fat type on vitamin C and vitamin E (alpha-and gamma-tocopherol) concentrations in peripheral and brain tissues and its effect on 8-epiPGF(2)alpha (F-2-isoprostanes). Male Golden Syrian hamsters (n = 120, 8 wk old) were fed diets enriched in butter, hydrogenated fat (margarine), and canola and soybean oils. After 12 wk, hamsters were deprived of food, anesthetized with isoflurane, and killed via terminal exsanguination. Analyses of vitamins C, E, and 8-epiPGF(2)alpha were performed in peripheral tissues and brain. Hamsters consuming the margarine-enriched diet had lower (P < 0.05) vitamin C and alpha-tocopherol concentrations in liver, plasma, and brain, and higher (P < 0.02) plasma 8-epiPGF(2)alpha than groups fed the butter, and the canola and soybean oil diets. Liver and plasma gamma-tocopherol concentration was higher (P < 0.001) among the groups fed the soybean- and margarine-enriched diets compared with the other groups. alpha-Tocopherol was higher (P < 0.05) and 8-epiPGF(2)alpha lower (P < 0.01) among the groups fed the canola and soybean oil diets compared with the other groups. Across the groups, an inverse correlation between plasma levels of vitamin C and 8-epiPGF(2)alpha (r = -0.37, P = 0.03) and a positive correlation between plasma levels of vitamin C and alpha-tocopherol were observed (r = 0.341, P = 0.003). Hamsters fed the butter-enriched diet had a higher (P < 0.03) plasma uric acid concentration than the other groups. The results of this study provide new evidence concerning the effect of dietary fat on antioxidant status, which is important for the maintenance of good health.