Many populations of amphibians are facing remarkable decline throughout the world. The reason for the decline is a direct response to habitat destruction and pollution including heavy metals. The blood of the toad is vascular and very plastic tissue. In fact, a variation of several hematological parameters in response to natural changes in the environment has been widely described previously. Since hematological parameters are influenced by a variety of environmental stressors, they have the potential to be used as biomarkers of aquatic pollution.  Heavy metals are difficult to remove from the environment and cannot be degraded biologically. The current study assessed the impact of some heavy metals on hematological and serological parameters in the Egyptian toad (Sclerophrys regularis) from two different localities (North Giza and El Wahat regions). The current results have revealed a reduction in the means of RBCs, hemoglobin, and hematocrit values in addition to a remarkable increase in WBCs. In addition, the major serological parameters including protein, albumin, AST, and ALT were also altered in parallel with the deterioration that occurred between the two investigated regions. The present findings have revealed and confirmed that the Abu Rawash area is more impacted compared to El Bawiti.