Nanoparticles (NPs) are used in diverse field of technology and consequently are released to the environment, most ending up in water bodies. Because NPs have potential to cause adverse effects on the metabolisms of animals, the present study was carried out to help understanding their effects on fish metabolism. In this study, freshwater fish (Oreochromis niloticus) were exposed to aluminum oxide (Al2O3) (40 nm), copper oxide (CuO) (40 nm) and titanium dioxide (TiO2) (21 nm) NPs in differing concentrations (0, 1, 5, 25 mg/L) for 14 d. Following the exposures, the levels of glucose, cholesterol, triglyceride, blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), Na+, K+, triiodothyronine (T3), thyroxine (T4) and cortisol in the serum of fish were measured. The results of this study showed that there were significant alterations in the levels of some serum parameters. The levels of glucose, triglyceride, BUN, creatinine, K+, cortisol and T4 in the serum were changed following NP exposures, though there was no statistical difference in the levels of cholesterol, ALT, AST, ALP, Na+ and T3. Most striking data were obtained in the levels of BUN and creatinine, as their levels increased nearly 10 folds. Transmission electron microscope (TEM) images showed NP accumulation in tissues of fish even at the lowest exposure concentration. This study emphasized that NPs are not innocent compounds and can have hazardous effects when taken in substantial levels, suggesting there must be some criteria and limits in their usage and discharge to the environment. Nevertheless, more studies are needed to understand better their toxicities in different classes of animals.