Oreochromis niloticus (Linnaeus, 1758) were exposed to Pb (0.1 and 1.0 mg/L Pb) and mixtures of 0.1 mg/L Pb+0.5 mg/L Se and 1.0 mg/L Pb+5.0 mg/L Se to investigate responses of serum biochemical parameters and Pb level of the blood over different exposure periods (7, 14 and 28 days). Activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, lipase, cholinesterase were analyzed in the blood serum samples. Cholinesterase activity decreased while other enzymes activities increased in Pb exposed groups. It was reported that Pb level in the blood tissue of fish exposed to Pb and Se mixture for 7, 14, 28 days was observed to be lower than exposing Pb alone. It could be concluded that Se supplementation may reduce the toxic effect of Pb in O. niloticus. The results of this investigation suggested the blood of fish could be used as a good target tissue to reflect toxic effects of Pb.