The objective of the present study was to evaluate the oxidative stress potential of mercury (Hg) exposure with the modulatory effect of selenium (Se) in the brain and kidney tissues of Oreochromis niloticus. The fish were exposed to 0.01 and 0.1 mg/L Hg, 0.01 mg/L Hg+0.1 mg/L Se, and 0.1 mg/L Hg+1.0 mg/L Se, for 7 and 14 days. The activities of total glutathione (tGSH), malondialdehyde (MDA) and catalase (CAT), glutathione S-transferase (GST), and acetylcholinesterase (AChE) were measured from samples of the tissues. The results indicated that all concentrations of Hg caused a time-dependent increase in CAT, GST activity, whereas AChE. activity and tGSH content were decreased in brain and kidney tissues. MDA levels in tissues of fish exposed to Hg+Se mixtures were lower compared to those exposed to Hg only. Selenium application in combination with mercury provided an alleviation of the toxic effects of mercury in the investigated tissues for biochemical parameters.