The predatory efficacy of tilapia Oreochromis niloticus was confirmed against the immature stages of mosquitoes including Culex pipiens. The present study evaluated the detrimental impacts of sublethal concentration of myclobutanil (1000 µg/L) and S-metolachlor (140 µg/L) pesticides for 15 days on the predatory potential of O. niloticus on larvae of Cx. pipiens. Also, effects of both pesticides on acetylcholinesterase (AChE), and certain antioxidant parameters (i.e., total antioxidant capacity [TAC] and superoxide dismutase [SOD]) in the fish were assessed. The exposure of O. niloticus to sublethal concentration of myclobutanil and S-metolachlor caused destructive effects on the predatory behavior of the fish and decreased its predation rates on mosquito larvae compared to the control. Changes in predation capacity of the predatory fish on mosquito larvae may be due to the toxic effect of these pesticides on fish’s antioxidants and AChE activity. The fish pre-exposed to both pesticides presented a significant decrease in the TAC and a significant increase in the SOD activity relative to control group, indicating the advancement of oxidative stress in the treated fish. Fishes pre-exposed to sublethal of both pesticides also showed a significant increase in AChE activity. This study suggests a threat of S-metolachlor and myclobutanil to O. niloticus health and potential as a successful indigenous predatory fish on Cx. pipiens larvae.