The present study was designed to reveal the relative impact of water quality changes induced by the climate's influence and some waste discharge on the existence and prevalence of some gill parasite species in the Nile tilapia inhabiting Rosetta Branch, the River Nile. Both fish (1600 Nile tilapia fish) and water samples were randomly collected seasonally from four sites (El-Kanater El-Khayria, El-Qatta, Tamalay, and Kafr El-Zayat) along the Rosetta Branch of the Nile, which receives some types of wastewater. Parasitological examination of fish revealed the presence of Trichodina sp., Ambiphyra sp., Cichlidogyrus tilapiae, the encysted metacercaria of Clinostomum phalacrocoracis, and the larval stage of the freshwater mussels, Glochidia. The highest parasite prevalence was recorded at Kafr El-Zayat station, followed by El-Qatta and Tamalay. On the other hand, the autumn season recorded the highest parasitic prevalence, followed by winter, summer, and spring. The histological examination of the gills of the infected fish revealed severe histological alterations and the presence of different histozoic parasites. The most significant water parameters influencing the parasitic prevalence were temperature, pH, DO, BOD, and ammonia. The outcomes reveal that water parameter, temperature, pH, DO, BOD, and TAN are important factors affecting the different parasite prevalence values of the infected tilapia fish.