The negative impact of point sources of pollution such as effluents from wastewater treatment plants (WWTPs) is a significant problem for freshwater ecosystems. Zooplankton can be used as indicators of the ecological status in rivers. Therefore, this study was carried out to investigate the effects of contaminants resulting from WWTPs discharges on abundance and diversity of zooplankton or community in River Nile, Assiut, Egypt. Four different sites were selected to perform the present study. The collection of water, sediment and plankton samples was carried out on the 31st of July 2022 (summer) and the 2nd of February 2023 (winter). A total of 30 zooplankton taxa have been recorded; the maximum share in zooplankton composition was shown by Rotifers (43.33%) followed by Meroplankton (20%), Protozoa (16.67%), Cladocera (13.33%), and least by Copepoda (6.67%). In the present study, some species of zooplankton disappeared or become scarce in the plankton composition in S (WWTPs drain) and J (where WWTPs mixed with River water) sites compered to R (upstream before the WWTPs discharge) and A (downstream after the WWTPs discharge) sites. Overall, the zooplankton structure of the river showed a diverse spatial distribution due to the influence of WWTPs discharge. This study highlights unprecedented information to understand how caffeine, Zn and some other physicochemical parameters may interact with aquatic environment, using the zooplankton commonly found in the aquatic habitat. Several WWTP treatment systems must be implemented or improved to reduce the discharge of contaminants from these point sources into the Nile River.