This dissertation is a social history of medicine, which examines how the economy ofcotton monoculture engendered malnutrition and its constituent disease, pellagra, in the early twentieth-century U.S. South. Pellagra is a nutritional disease caused by a deficiency of the vitamin B3 (niacin). Between 1906–1941, nearly three million people experienced pellagra as a direct result of the seismic social and economic disruptions generated by the dominance, and ultimately the decline, of cotton monoculture. When officials from the U.S. Public Health Service, namely Dr. Joseph Goldberger, articulated the structural economic determinants of the disease, the assertion proved deeply controversial and exposed a rift in the southern medical community, which continued to believe that pellagra was an infectious disease rather than a disease of poverty. Cotton monoculture produced abysmal wages, violent working conditions, racial disfranchisement, limited access to nutritive foods, and a paucity of healthcare infrastructure among the South’s most marginalized communities. Pellagra was so intimately bound to the cotton economy that public health officials began charting predictions in the average purchase price of cotton in order to predict the severity of the South’s recurrent pellagra epidemics. "Epidemic Economy" examines not only how cotton monoculture made southern workers sick with pellagra, but also how the cotton economy writ large shaped public health infrastructure across the long twentieth-century U.S. South.