Fresh water edible crab, Barytelphusa guerini were exposed to acute dose of mercury chloride and copper sulphate. The aim of investigation was to evaluate the effect of heavy metal, HgCl2 and CuSO4 on the lipase activity in hepatopancreas of B. guerini. The effects were observed and studied seasonally into two groups as control and experimental. At the end of 96hrs the crabs were removed and hepatopancreatic tissue was separated to prepare enzyme extract for assay purpose. The results are reported as unit lipase activity /gm of tissue/ hr at 37oC. In the present investigation, the lipase was significantly altered and progressive decrease in activity was observed due to inhibitory action of HgCl2 and CuSO4. Among the exposed mercuric chloride was found to be more potent inhibitor of lipase activity as compared to control group and copper sulphate induced group. From the results, it is also observed that the enzyme activity is time dependent i.e. summer>winter>monsoon.