To study the combined effect of the flavonoid quercetin and fish oil containing ω-3 fatty acids on preventing diet-induced metabolic syndrome, we fed mice with a control diet, a high-fat, high-sucrose, and high-cholesterol Western-style diet (Western diet), a Western diet supplemented with 0.05% quercetin, a Western diet containing 5% fish oil rich in docosahexaenoic acid (DHA) (DHA diet), or a DHA diet supplemented with 0.05% quercetin. After 18 weeks of feeding, fish oil potentiated the suppression of lipid peroxidation by quercetin in the liver but not in the epididymal adipose tissue. Fish oil but not quercetin suppressed the accumulation of non-esterified fatty acids and the expression of fatty acid synthase in the liver of Western-diet-fed mice. Thus, the combination of quercetin and DHA-rich fish oil may partly alleviate non-alcoholic fatty liver disease by reducing oxidative stress and suppressing fatty acid synthesis.