We investigated that the synergistic toxicity of thiamethoxam and lambda cyhalothrin on total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OXI) and protein content in liver, brain and gonad tissues as well as somatic indices of Oreochromis niloticus. The fish exposed to 1/20, 1/10 of 96h LC50 value of thiamethoxam and lambda cyhalothrin (477.29 mg/L, 2.901 mu g/L), individually and in mixtures, for 7 and 15 days. Fish were then left to depurate for 7 days in pesticide-free water. Total oxidant status and OXI increased while TAC decreased in tissues. Hepatosomatic (HSI) and gonadosomatic indices (GSI) were found lower than control group while condition factor did not show any difference. The combined treatments of pesticides exerted synergistic effects on OXI. Increased TOS/OXI, decreased TAC, HSI, GSI and alteration in protein level have shown that pesticides cause generation of free radical formation and start oxidative damage in tissues. Also, depuration period for 7 days was not adequate to eliminate the toxic effects of pesticides. Therefore thiamethoxam and lambda cyhalothrin may be considered as risky aquatic organisms.