Technical Abstract: Research examined the effects of mannan oligosaccharide (MOS, Alltech, Inc., Nicholasville, KY) as a potential feed additive in channel catfish. In the first study, MOS was fed at 2 g/kg diet for six weeks followed by challenge with Edwardsiella ictaluri, the bacterium that causes Enteric Septicemia of Catfish (ESC). All fish were bled pre- challenge as well as on day 14 of the challenge. In a second study, MOS was fed at 4 g/kg diet for nine weeks followed by challenge with E. ictaluri. Mortalities were collected for 21 days. Gut morphology was examined in fish fed MOS as well as controls prior to challenge. Sections of the distal, middle, and proximal parts of the intestine were taken for analysis. Feeding MOS at 2 or 4 g/kg diet for six or nine weeks did not improve weight gain, specific growth rate, or food conversion ratio. However, survival was significantly increased after challenge with E. ictaluri in both studies (P < 0.05). Plasma levels of lysozyme were similar in MOS fed fish pre- and post-challenge. Microvilli lengths in all sections of the intestine were similar in all treatments after 9 weeks of feeding. Although channel catfish fed MOS demonstrated improved survival after bacterial challenge, the mechanisms through which MOS improved survival were not determined in these studies.