Technical Abstract: Enteric septicemia of catfish (ESC) and columnaris, the most common channel catfish Ictalurus punctatus diseases in the southeastern United States, are caused by the bacteria Edwardsiella ictaluri and Flavobacterium columnare, respectively. Although producers may rely on antibiotics and certain therapeutants to help manage these diseases, the discovery of new compounds that are environmentally safe and efficacious alternatives to current antibiotics and therapeutants would benefit the catfish aquaculture industry. A rapid bioassay was used to evaluate compounds as the first step in the discovery process. Tannic acid was found to be highly toxic towards E. ictaluri and F. columnare, and it appears to be promising for future efficacy testing against ESC and columnaris. Sodium percarbonate, an environmentally-safe compound, appears to be promising for future efficacy testing to determine its potential use in managing and preventing F. columnare outbreaks in small-scale systems used to culture catfish or during the transport of catfish.