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Heavy metals are frequently encountered as mixtures of essential and non-essential elements. Therefore, evaluation of their toxic effects individually does not offer a realistic estimate of their impact on biological processes. We studied effects of exposure to mixtures of essential and toxic metals (Cr, Cd and Pb) on biochemical, immunotoxicity level and morphological characteristics of the various tissues of a biomarker freshwater fish common carp using environmentally relevant concentrations. Fish were exposed to metal mixture through tank water for 7, 15 and 30 days, under controlled laboratory conditions. Tissue accumulation of the metals was measured using Atomic Absorption Spectrophotometric techniques. Chromium, cadmium and lead accumulation in muscle, gills, liver, kidney and intestine, tissue of common carp exposed to mixture metals for 30 days increased significant compared with control group (p < 0.001). However, the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) levels was significant altered in various tissues of exposed fish. Besides, the lipid peroxidation (LPO) was significant (p < 0.001) increased. Moreover, the tumor necrosis factor - α (TNF-α), interleukin (IL-6), and interferon-γ (IFN-γ) contents in tissues of muscle, gills, liver, kidney and intestine were increased significant compared with control fish (p < 0.001). In addition, microscopic examination of the main alterations in general morphology of fish gills included spiking and fusion of secondary lamellae, formation of club-shaped filaments epithelium in the interlamellar regions and hepatocytes showed damage of central vein and rupture of irregular hepatic plate with more number of vacuoles in the fish exposed to metal mixture for a longer duration (30 days). These results of this study clearly demonstrate that concentration individual and mixtures of metals in aquatic systems will greatly influence the cytokine alterations may result in an immune suppression or excessive activation in the treated common carp as well as may cause immune dysfunction or reduced immunity. In conclusion, toxicity of multiple metal mixtures of Cr, Cd and Pb has antioxidant and immunotoxic effects on C. carpio. [ABSTRACT FROM AUTHOR]