A seasonal study was performed on the wild Oreochomis niloticus collected seasonally from Suez channel, branched of the River Nile in Fayed region, Ismailia Governorate in Egypt. Specimens were addressed to investigate the role of natural infestation with parasites in secondary infection with Aeromonas and Vibrio species in a combination with unfavorable environmental conditions. Acanthocephalans (Acanthocentis tilapiae and Neoechinorhynchus sp.) and trematode/ digenean Euclinostomum heterostomum were isolated from the intestine and kidneys of O. niloticus, respectively. Aeromonas hydrophila, Vibrio alginolyticus, and Vibrio parahaemolyticus were isolated from different organs of some examined tilapias and identified biochemically by VITEK®2 compac system and by PCR. The water quality parameters were significantly elevated over the permissible levels, whereas an annual average elevation was detected in nitrite (0.06 ±0.08 mg/L) and un-ionized ammonia (0.31 ±0.29 mg/L). The prevalence of co-infections of Motile Aeromonas Septicemia (MAS) with acanthocephalan was the highest in summer season (33.3%). Additionally, the vibriosis with acanthocephalan infestation was the highest in summer (66.7%) and the lowest in winter (10.0%) in both cases. While co-infection of MAS with Euclinostomum heterostomum infestation together with the vibriosis were recorded the highest in summer with 50% and 100%, respectively, and the lowest was in winter (00.0%) in both cases. Histopathological alterations were recorded in different organs as gills, liver, kidney and spleen in affected fish. It could be concluded that bad water quality and parasitism may depress immunity and stress fish facilitating Aeromonas and Vibrio infections.