The distribution of pesticides in water, sediments, Clarias gariepinus, and Procambarus clarkii from Muweis canal at two localities was investigated to evaluate the pollution status and potential hazard in the river system. A total of 28 pesticides were analyzed using gas chromatography (GC) with electron capture detector. The concentration of pesticide residues ranged from ND (not detected) to 0.560mg/l for water samples, ND to 0.73 μg/g dw for sediment, ND to 9.653 μg/g ww for C. gariepinus, and ND to 6.875 μg/g ww for P. clarkii. High concentrations of organochlorine pesticides, specifically fenpropathrin, endosulfan ii, delta-BHC and dieldrin observed in all environmental media, are an indication of the current illegal use of banned pesticides for agricultural activities in the region. Tal-Haween water samples revealed the highest content of pesticides followed by El-Shabakat water, while the sediment of Tal-Haween observed more contaminated than that of El-Shabakat. Also, C. gariepinus exhibited more polluted than P. clarkii. Analysis of data showed significant differences between gills of C. gariepinus, water and sediment samples of Tal-Haween site in fenpropathrin and endosulfan ii respectively, while exhibited a highly significant difference between water and sediment samples of El-Shabakat site in aldrin. Moreover, there was a highly significant difference in correlation coefficient between water and sediment samples of El-Shabakat site in endosulfan ii and endrin. Concerning the mean concentrations of some pesticides in water and fish, the levels were higher than that recommended by the international permissible limits. It is an indication of a potential cancer hazard for the local inhabitants with lifetime consumption of pesticide-polluted fish.