Measurement of serum biochemical parameters in response to metal exposures can be especially useful to help identify target organs of toxicity as well as the general health status of animals. Oreochromis niloticus were exposed to 5.0 mg/L Zn, 1.0 mg/L Cd, and 5.0 mg/L Zn + 1.0 mg/L Cd mixture for 7 and 28 days, and alterations in serum enzyme activities and ion levels were measured. Significant changes in all the biochemical parameters were found to be time dependent. Following metal exposure, alkaline phosphatase activity was elevated at both exposure periods. No changes in activities of lactate dehydrogenase and lipase were observed in response to single or combined Zn and Cd exposure at 7 days while they increased at 28 days. Fish exposed to metals showed a decrease in cholinesterase activity at 7 days followed by a return to control levels at the end of the exposure period. The individual and combined effects of metals caused a decline in levels of Na(+), Cl(-), and Ca(2+), especially at 28 days. K(+) level increased at 7 days but it returned to control levels with increasing duration of exposure. This study indicated that the alterations in serum parameters may be a result of the target tissue (i.e., liver, gill, and kidney) damage and dysfunction induced by the metals and that these parameters can thus be used to assess the effects of metals on organisms.