The present study aimed to assess the toxic effect of lead and mercury on aquatic sources as it indirectly or directly affects human beings. A freshwater Catfish Clarias batrachus was chosen as an ideal model for the experiment, as it can survive in unfavourable conditions. Sub lethal toxicity studies of lead and mercury on the Indian freshwater Catfish revealed significant changes in the biochemical constituents of the fish like total protein and glucose after 15 days of exposure to different lead acetate concentrations i.e. 0.2mg/l, 0.6mg/l and 1mg/l; the mercury chloride concentrations i.e. 0.0002mg/l, 0.002mg/l, and 0.02mg/l. Liver, kidney, gill and muscle tissues of control of treated fishes were taken for the protein estimation and blood samples of control and treated fish were considered for estimation of glucose. Depletion of protein was observed in various tissues of the treated fish as compared to the controlled fishes. The progressive elevation of plasma glucose level was observed in treated fish as compared to the controlled fishes in case of both lead and mercury treatment. The current findings suggest that the fish treated with lead have faced a serious metabolic crisis that also observed as nearly equivalent to the fish treated with a very low concentration of mercury.