Mixed pollution of the freshwaters is a worldwide problem; and the scientific evidence showed its impacts on the bivalves` biological processes. In the present study, the freshwater clam, Caelatura nilotica was collected from two water habitats with different degrees of pollution. Examination of gills and digestive gland using routine histology, scanning (SEM), and transmission (TEM) electron microscopy was done. In SEM investigations of the gills, deformation and erosion of cilia, clogging of gills by mucous and ghost gills were observed in the clams collected from a more polluted site. Histological structure of gills proved the appearance of ciliates between the gill filaments. Also, inflammatory reactions appeared and the epithelia lost their integrity and desquamated. The digestive gland showed haemocytes infiltrations, necrosis in some digestive tubules, and granulocytomas was observed. A full description of the digestive gland was done using TEM. In addition, more abnormalities were recorded in different types of the haemocytes, digestive and basophilic cells, flagella, microvilli, lysosomes, residual bodies, mitochondria, nucleus and chromatin with blebbing in most of them. In conclusion, mixed pollution compromised the functions of the gills and digestive gland of the clam, C. nilotica, under the effect of synergistic and/ or antagonistic actions of inorganic and organic contaminants with reference to the more severe effects of the non-point source than the point-source pollution in water pollution impacts.