Tilapia production from aquaculture is growing fast in Uganda to meet the increasing demand for fish. Farm yields and profits are increasingly reduced by periodic disease outbreaks in land and water-based systems. High mortalities experienced within hatcheries and cage systems with infected fish presenting signs of lethargy, exophthalmia, granulomatous spleen, fin rot, ulcerations and haemorrhages. Histopathological reports showed gill hyperplasia with epitheliocystis, and granulomatous head-kidney, spleen, liver with melanomacrophages. However, asymptomatic fish samples showed recovery stages of populations as exhibited in granulomas spleen and kidney. Molecular identification revealed unique strains of Aeromonas veronii, A. hydrophila of Edwarsiella ictaluri, E. anguillarum, Francisella philomiragia, F. noatunensis and F. tularensis from infected farmed tilapia in Uganda. These were resistant to Ampicilin and Amoxicillin, erythromycin and sulphamethoxazole trimethoprim, respectively. Identification of co-occurrence of these emerging pathogens presents strategies to reduce further economic losses in the tilapia industry.