Corn production in the US is the biggest in the world. Accordingly, the nation utilizes corn in various products including ethanol production and the co-products recycling into animal feed. Fermented corn protein (FCP) is a high-protein, low-fiber improved co-product of the ethanol industry. The fermented ingredient is rich in lysine and methionine and contains fewer antinutritional factors, which makes it a potential candidate to replace or complement soybean meal whilst improving animal growth and health. Accordingly, the present work assesses the effects of FCP on channel catfish growth, whole body composition, overall health and resistance to major disease-causing bacteria. Six diets were formulated at 32% protein and 6% lipid and included FCP as a partial substitute for soybean meal at 0, 5, 10, 15, 20, and 30%. After feed preparation, 20 channel catfish fingerlings (average individual weight = 2.56±0.06g) were stocked in 80L glass aquaria, part of a recirculating aquaculture system. Experimental diets were randomly assigned to six replicate aquaria, and the experiment was performed for 70 days. The fish were weighed bi-weekly, and the feed ration was calculated as a percentage of the aquarium biomass and increased by 10% the next week. At termination, fish were group weighed and enumerated, then two fish per tank were euthanized and preserved at -20℃ to be analyzed for whole body proximate composition. Additionally, three fish from each aquarium were anesthetized, and blood was collected for lysozyme activity and serum biochemistry analyses. Subsequently, another set of fish (average initial weight = 5.29±0.19g) was stocked into 24 glass aquaria, part of a similar system as above, at 63 fish per aquarium. Diets were randomly assigned to four replicate aquaria, and fish were acclimated to the diets for 42 days. Afterwards, fish were challenged by immersion with virulent Aeromonas hydrophila, Flavobacterium covae, and Edwardsiella ictaluri (dose in water of 3.55×107 CFU mL-1, 1.00×106 CFU mL-1, and 1.60×105 CFU mL-1, respectively). Results of the present work suggest FCP can be successfully used at 30% of channel catfish diets without adverse effects on fish growth, survival, protein retention, and whole body proximate composition (p>0.05). Additionally, the use of FCP did not significantly impact fish lysozyme activity or serum biochemistry, with the exception of total bilirubin. Moreover, bacterial challenge results infer that the inclusion of FCP in channel catfish diets at 15 to 20% can confer protection against infections with E. ictaluri. Fermented corn protein can successfully replace soybean meal in channel catfish diets, with a potential to protect the fish against E. ictaluri infections.