Omega-3 fatty acids were used in the treatment of psychiatric diseases such as bipolar disorder. Na(+), K(+)-ATPase is also a well-known target for these fatty acids. In this study, we investigated the impact of cod-liver oil (CLO), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on Na(+), K(+)-ATPase, cholinesterase activities, the levels of norepinephrine (NE) and acetylcholine in different regions of rat brain. Our results showed that DHA caused a significant depression in cerebellum Na(+), K( +)-ATPase, whereas CLO activated it. In addition, CLO, EPA and DHA produced a significant activation in Na(+), K(+)-ATPase activity in medulla, midbrain and hypothalamus. There were non-significant changes in the activity of cholinesterase enzyme in cerebellum and medulla, while in midbrain and hypothalamus the CLO, DHA and EPA enhanced the activity by 75%, 100% and 78%, respectively. The content of NE in hypothalamus showed slight increase in different regions of the brain of animals fed CLO, DHA or EPA. In conclusion, CLO, DHA or EPA supplementation had a beneficial effect that associated with a normalization of fatty acids incorporation into phospholipid membranes and a partial restoration of Na(+), K(+)-ATPase activity, suggesting that CLO supplementation may improve fatty acid composition and moderately enhance Na(+), K(+)-ATPase activity.