In current research, the combined effects of copper oxide nanoparticles (CuO NPs) and titanium dioxide nanoparticles (TiO2 NPs) on the histopathological anomalies of gill and intestine tissues in common carp (Cyprinus carpio) were studied. Common carp were exposed to TiO2 NPs (10.0 mg L−1), CuO NPs (2.5 and 5.0 mg L−1), and mixture of TiO2 NPs (10.0 mg L−1) + CuO NPs (2.5 and 5.0 mg L−1) for two periods of exposure (10 and 20 days) and recovery (30 and 40 days). The most common histopathological anomalies in the gill of common carp such as hyperplasia, oedema, curvature, fusion, aneurism, and necrosis were observed. The synergistic effect of co-existing TiO2 NPs and CuO NPs reduced the length of secondary lamella and increased the diameters of the gill filaments and secondary lamellae. Moreover, the presence of TiO2 NPs increased the CuO NPs effects on the histopathological anomalies of intestine tissue and the synergistic effect of TiO2 NPs and CuO mixture leads to an increase in the severity of histopathological lesions such as degeneration, swelling of goblet cells, and necrosis - erosion in the intestine tissue. In conclusion, the presence of TiO2 NPs increased the toxicity of CuO NPs.