Following the toxicity and potential risk posed by the heavy metals to man and aquatic ecosystems, the study investigates the adverse changes exerted by sublethal concentrations of triple mixture of heavy metals (Cd, Cr, and Pb) on the glycogen and vitamin E reserves of tilapia species, Oreochromis niloticus over an exposure period of 1, 10, 20, and 40 days. The investigation consists of control group of fish maintained in normal water while the experimental group was exposed to 4.5mg/l triple mixture of Cd, Cr, and Pb solution at 1.5mg/l each of the metals for the period of exposure. Both groups were compared at the end of the experiment to measure deviations. Glycogen and vitamin E levels measured in the fish liver homogenates decreased (P<0.05) consistently over the experimental period and there were significant (P<0.05) variations between the exposure days, all at 95% confidence limits. The sensitivity of biochemical markers has been of vital application in environmental monitoring and the current research attesting to it, calls for proactive response and regulations to pollution due to heavy metals resulting from various anthropogenic activities.