This study aimed to investigate concentrations of organochlorine pesticides (OCPs) residues in muscles of different fish species; mullet, Nile tilapia, and catfish obtained from different locations (Nile River, Wadi El-Rayan Lake, Edku and Burullus lagoons) during July 2019. Also, it aimed to study the effect of the grilling process on these concentrations in Nile tilapia as abundant fish.  Results showed that 15 compounds of OCPs were identified in raw fish samples and grilled tilapia. Concerning fish species, mullet from Edku, tilapia from Burullus, and catfish from Wadi El-Rayan were the lowest polluted than other ones. With regard to the location of catch, the Nile River was mostly polluted with OCPs and Wadi El-Rayan  followed by Burullus and Edku lagoons. On the other side, grilling process reduced all compounds of OCPs; the loss rate in grilled tilapia was taken the following order; ∑HCH (72.59- 97.08%) >∑DDT (61.52- 94.94%) > ∑Heptachlor (58.37- 87.53%) > ∑Endosulfan (50.98-79.17%) > Endrin (32.06-83.95%) >∑Aldrin (21.15-100%). In conclusion, this study proved that concentrations of OCPs compounds in raw fish muscles were lower than the maximum permissible limits (MPLs), and grilling decreased sharply all OCPs compounds. So, the muscles of raw and grilled investigated fish samples were considered safe for human consumption.