The histological lesions caused by Edwardsiella tarda in a variety of fish species, including tilapia, have been well characterized. There are apparent differences in the type of inflammatory response manifested by these different species, which may be due to the fish species itself, the phase of infection, or the virulence factors produced by different strains of E. tarda. In catfish, systemic abscesses involving muscles of the flank or caudal peduncle are the most common lesions. By contrast, infection in tilapia and red sea bream is more likely to be associated with granulomatous inflammation. Necrotic meningitis, encephalitis, and vasculitis with fibrinoid necrosis of the blood vessels walls, as well as the formation of a plaque-like structure in the brain, are described in the current study. The presence of E. tarda was confirmed by microbiological isolation and a positive nested polymerase chain reaction in paraffin wax–embedded tilapia tissues.