This work describes the parasitic infections in wild Synodontis serratus and Synodontis schall from Lake Nasser, Egypt and the histopthological impacts of these parasites on the infected fish. A total number of 100 Synodontis serratus and100 Synodontis schall were collected alive from several and various localities of the lake during 2018. One cestode: Wenyonia virilis, three nematodes: Cithariniella citharini, Procamallanus laeviconchus and Spirocamallanus pseudospiralis (new locality record) and one zoonotic encysted metacercaria of trematode: Centrocestus formosanus (new hosts record) were identified from both fish species; in addition to, one cestode: Proteocephalus sulcatus and one acanthocephalan: Rhadinorhynchus sp < em>. (new host record) were only recorded from Synodontis schall. The infection rates of examined fish; Synodontis serratus and Synodontis schall were 54% and 78% respectively. This study evaluated clinical signs, postmortem lesions, organ or tissue susceptibility, incidence, intensity of infection, seasonal prevalence and histopathological alterations induced by these parasitic infections. Interestingly, the musculature of the fish was free from any parasitic infections and safe for human consumption provided that the fish would be eviscerated and adequately cooked. This work provides analysis of fish-parasite fauna which is a very helpful tool for implementing control and preventative measures against parasitic diseases especially the zoonotic ones.