Technical Abstract: In a continuing effort to discover natural products and natural product-based compounds for the control of columnaris disease in channel catfish (Ictalurus punctatus), seventeen lycorine analogs were synthesized, including new benzoyl analogs 6 – 16, and evaluated for antibacterial activity against two isolates (ALM-00-173 and BioMed) of Flavobacterium columnare using a rapid bioassay. Two of the lycorine analogs had greater antibacterial activity than 1-O-acetyllycorine, an analog of lycorine evaluated previously that is highly active against both isolates. Carbamate analog 18 (1S,2S,3a1S,12bS)-2,3a1,4,5,7,12b-Hexahydro-1H-[1,3]dioxolo[4,5-j]pyrrolo[3,2,1-de]phenanthridin-1,2-diyl-bis(o-tolylcarbamate) had the strongest antibacterial activity towards both F. columnare isolates ALM-00-173 and BioMed, with a 24-h IC50 of 3.0±1.3 mg/L and 3.9±2.2 mg/L, respectively, and a MIC of 5.5±0 mg/L for both isolates. Compound 18 appears to be the most promising lycorine analog for future efficacy studies to determine its potential for use as an alternative to the currently used compounds to control columnaris disease in channel catfish.