One hundred and fifty O. niloticus (35±0.5g) were collected from Abbassa Fish Hatchery, Sharkia, Egypt to determine the changes in immune parameters (after 15 and 30 days) of Oreochromis niloticus exposed to Organophosphrous insecticide (Chlorpyrifos) and infested with Cichlidogyrus sp. In addition, this study was carried out to evaluate the effect of the Chlorpyrifos exposure on the intensity and vitality of Cichlidogyrus sp. Chlorpyrifos decreased significantly both parasitic intensity and vitality. Serum total proteins, albumin and globulin were significantly decreased in both infested group and infested ones with pesticide exposure. Serum IgM level was elevated in infested group after 15 days of the experiment and decreased after 30 days of the experiment. Serum lysozyme and nitric oxide were elevated in all experimental groups after 15 and 30 days of the experiment. While phagocytic % and Phagocytic index were significantly decreased in all experimental groups after 15 and 30 days of the experiment. The expression of IL-1β were significantly increased after 15 days of the experiment, while both infestation and Chlorpyrifos exposure showed no significant differences after 30 days. In conclusion, infection with Cichlidogyrus sp. in fish exposed to Chlorpyrifos pollution had the highest drastic effect on the health and immune status of fish.