Nowadays, and due to different anthropogenic activities, the environmental conditions deteriorate and consequently productivity of cultured and wild fish decreases. The present study highlights the role of effective microorganisms (EM) as a probiotic in enhancing biological features and growth performance of the cultured Nile tilapia (Oreochromis niloticus) exposed to copper metal under experimental conditions. Other metals that may interfere with toxic effects of copper on fish were measured. The conducted toxicity test showed that the copper 96hr LC₅₀ is 6.30 mg/l, thus fish of the experimental groups were exposed to 0.1 of that dose (0.630 mg/l) as a sublethal chronic dose for 12 weeks. After this long-term exposure period, metal concentrations in gills, liver, kidney, muscles and skin of O. niloticus showed significant increase in the copper exposed group associated with histopathological changes and clear damage in gills, liver and kidney tissues comparing to the EM exposed group. Moreover, the results revealed significant improvement in growth indices, histological and biochemical aspects of EM exposed fish. The present study recommends the use of effective microorganisms in fish farms to enhance fish productivity and reduce the toxic effects of pollutants.