Henneguya ghaffari Ali (Dis Aquat Org 38:225-230, 1999), which was originally described in Lake Wadi El-Rayan in the western desert of Egypt, has been discovered in the gills of the Nile perch, Lates niloticus, sourced from the River Nile at Beni-Suef governorate. The species identification was based on the spore morphometry. Of 180 Nile perch, 68 were found to be naturally infected with H. ghaffari (37.7%). A significant seasonal fluctuation in the prevalence was discerned, with the maximum rate occurring in the winter (68.8%) and the minimum rate in the summer (8.8%). The plasmodia of the parasite were evident as white rods, occupying almost a third of the gill filament and with mean dimensions of 0.7 × 0.2 mm. Histological investigations revealed that the present plasmodia were potentially compatible with the intrafilamental type. Infection with H. ghaffari initiated epithelial hyperplasia and curling and atrophy of the respiratory lamellae, which underpin its deleterious effect on the host by decreasing the functional respiratory surface of the gills. The present study concluded that infection with H. ghaffari originated in the River Nile before moving to the new ecosystem of Lake Wadi El-Rayan through drainage water.