In July 2001, a great egret (Casmerodius albus) was found dead in Charlton County, Georgia (USA) and submitted to the Southeastern Cooperative Wildlife Disease Study (The University of Georgia, Athens, Georgia). Histopathologic findings included severe hepatic necrosis and necrosis of sheathed arterioles. Eastern equine encephalitis (EEE) virus was isolated from brain and heart using Vero cells and was identified using a standard micro-neutralization test and reverse transcription polymerase chain reaction (rtPCR). Streptavidin-biotin alkaline phosphatase immunohistochemistry using mouse anti-EEE virus monoclonal antibody demonstrated EEE antigen within cells of the sheathed arterioles and scattered mononuclear cells in the splenic parenchyma. To the authors' knowledge, this is the first description of natural infection and pathologic effects of EEE virus infection in a great egret.