Mesozooplankton abundance and distribution at Damietta Branch, Nile River was studied to assess the impacts caused by human activities. The sampling was done monthly at seven stations during October 2013-September 2014. A plankton ring net with 180 µm mesh size was used to avoid the bias toward the collection of smaller mesozooplanktons such as rotifers and copepod larvae. Thirty-six mesozooplankton taxa were recorded. Cladocera was the most abundant group (41.6%), followed by Copepods (29.9%), Rotifera (14.8%), and Ostracoda (13.2%). The decrease in rotifers density in favor of copepods and cladocerans in the ROT:CLA:COP ratio suggesting an increase in the area eutrophication. According to SIMPER analysis, the most important taxa were Bosmina longirostris, Ceriodaphnia reticulate, Moina micrura, Acanthocyclops americanus, Brachionus calyciflorus, and Candona subgibba. Multivariate analysis indicated that the variations in species distribution were associated with environmental factors, especially water temperature, conductivity, and nitrate. The degree of anthropogenic disturbance determines the quality and quantity of plankton in the study area. Consequently, the discharged post-cooling waters should be controlled to protect zooplankton fauna and in consequence the planktivorous fish of the study area.