Background: Soil heavy metal pollution is an important environmental concern that has serious adverse effects on soil biota. The present study is aimed to assess the toxicity of heavy metals; lead (Pb) and nickel (Ni) on the biochemical and immunological parameters of Eudrilus eugeniae. Methods: Adult earthworms were exposed to various sub-lethal concentrations of Pb and Ni along with their combinations. After exposure for a period of 90 days, the content of bio-molecules such as carbohydrates, crude lipids and crude proteins; the total number of coelomocytes and the number of different types of coelomocytes were determined. Result: The results showed that the bio-molecular content decreased gradually and the maximum decrease was recorded in T6 (Pb 0.06 ppm) followed by T9 (Ni 0.03 ppm+Pb 0.03 ppm). Similarly, a decline in the total number of coelomocytes and the number of different types of coelomocytes was observed in a dose-dependent manner. Structurally five different types of coelomocytes were distinguished: granulocytes I, granulocytes II, amoebocytes I, amoebocytes II and eleocytes. So, it can be concluded that heavy metals are highly toxic to earthworms and biochemical and immunological parameters can be used in environmental monitoring programs.