Aim: This study investigated the effects of pollutants on the biochemical and histopathological components of Papyrocranus afer obtained from the Banegbe River at different locations (upstream, middle-stream, and downstream). The effect of the pollutant on the checked were, levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in blood samples of the fishes and the histopathologic alterations of the gills and liver of the fishes.                                                                               Methodology: The gills and liver tissue of the fish were collected and processed using routine histologic techniques for fixing and embedding in paraffin and staining sections with hem eosin. All the indices of the enzyme tests were estimated with the aid of Randox Diagnostic Test Kits following the manufacturer’s methods.                                 Results: Evaluation of the plasma enzymes showed significant increases (p<0.05) in plasma ALT, AST, and ALP activity in all the sampled points of Banegbe River when compared to the control 1 (Orogodo river) with middle-stream having significant (p<0.05) higher concentrations when compared to down-stream and up-stream. The main alterations observed in the liver of the fish at the Banegbe River were Kupffer cell hyperplasia and focal necrosis of the liver. While the gills showed alteration of the structure of the epithelium, hyperplasia of the epithelium of the primary lamella, epithelial lifting, vacuolization, alteration of the structure, and occurrence of aneurysms in the secondary lamella, all these alterations were as a result of pollutant in the river. Control 1 showed normal parenchymal cells of the liver and normal gill structure.    Conclusion: The increase in enzyme activities suggests leakage of these enzymes from the liver cytosol into the bloodstream as a result of liver damage by contaminants. From our results, it can be concluded that the Banegbe River is polluted as a result of effluents channeled in the river by industries within the environs.