In this study, ninety fish samples showing clinical signs of septicemia were collected from two private fish farms of Oreochromis niloticus; forty fish were sampled from fayoum and fifty were from sharkia governorate, Egypt, during four seasons (autumn 2018 to summer 2019). The sampled diseased fish represented 10% of the fish, showing clinical signs and the mortality rate along the year was 15 %. In the postmortem examination, the signs of septicemia on the affected fishes were clear in most of the internal organs. The histopathological results were fully described in different organs of the affected fish. Bacteriological examination revealed isolation of Aeromonas hydrophila with prevalence rate along the year 77.33 % with the highest prevalence in summer (100%) in El Fayoum and it was 29.72 % along the year with the highest prevalence in autumn 33.33% in El Sharkia governorate. Vibrio vulnificans in El Fayoum governorate was not isolated but it was isolated from El Sharkia with prevalence rate of 16.22%; with the highest prevalence in autumn (33.33%,). Proteus vulgaris was identified in both governorates with overall prevalence rate of 6.67% in El Fayoum and the highest prevalence was recorded in both autumn and spring seasons (11.11%). In El Sharkia it was 27.03% but with the highest prevalence in summer (100%). Pseudomonas aeruginosa was also recorded with the prevalence rate of 20% along the year in El Fayoum governorate with the highest prevalence in winter 55.56% and it was 27.03% in El Sharkia governorate with the highest prevalence in winter 43.75%. In antibiotic sensitivity testing, each microorganism showed resistance against erythromycin except Vibrio vulnificus that showed sensitivity. Aeromonas hydrophila and Proteus vulgaris showed resistance to colistin sulphate and susceptibility to sulpha-trimethoprime. Vibrio vulnificus and Pseudomonas aeruginosa showed resistance against sulpha-trimethoprime and sensitive against colistin sulphate.