In this study, the effects of 1/10 and 1/20 96 h LC₅₀ of copper and lead on ectoparasitic infested Oreochromis niloticus (O. niloticus) were evaluated by measuring its impact on the intensity and vitality of Cichlidogyrus and Trichodina species. In addition, copper and lead effects on hematological, biochemical parameters and histopathological findings of infested O. niloticus gills were evaluated. Three hundred naturally infested O. niloticus with Cichlidogyrusand Trichodina species were divided into five equal groups, each with three replicates (20 fish/ replicate). The infested fish of the first group were kept as control. While, infested fish of the second and third groups were exposed to 1/10 (0.43 mg/L) and 1/20 (0.21 mg/L) of 96 h LC₅₀of copper sulphate, respectively. Fish of fourth and fifth group were exposed to 1/10 (20.2 mg/L) and 1/20 (10.1 mg/L) of 96 h LC₅₀ of lead acetate, respectively. The results revealed an inverse relationship between the different concentrations of copper and lead (1/10 and 1/20 96 h LC₅₀) and the intensity of external parasites in the gills of fish where the increase of copper and lead concentrations resulted in decrease in the intensity and vitality of ectoparasites during the experimental period (30 days). Red blood cell count, platelets, mean corpuscular volume, mean corpuscular hemoglobin, lymphocyte, neutrophil, esinophil, Aspertate Transminase; Alanine Transferase, urea and creatinine showed the lowest significant value in groups 2 and 4 in comparison to group 1, besides, histopathological alterations, such as; congestion of blood vessels and fusion of secondary lamellae and complete absence of secondary lamellae in gills of the experimental groups. It could be concluded that, fish ectoparasites (Cichlidogyrus and Trichodina species) are considered as a biomarker for environmental pollution (copper and lead pollution).