The price and availability of several feed commodities were heavily affected by recent global events, such as supply chain issues caused by the pandemic and the conflicts in Europe. With that in mind, the use of fermented corn protein (FCP) can be a promising alternative ingredient to replace soybean meal (SBM) in aquafeeds , because of its attractive price and constant supply . FCP is a by-product from the ethanol industry, and depending on the fermentation process, it can generate a high protein (>50 %) ingredient, with a relatively well-balanced amino acid profile, and low fiber content (~7.3 %). The present study evaluated the nutrient and energy digestibility of FCP by channel catfish, followed by a comparative feeding trial with juvenile channel catfish evaluating graded levels of replacement of dehulled solvent extracted SBM replacement with FCP in experimental feeds . T he digestibility study was performed using the indirect method, with experimental feeds supplemented with 0.1% of yttrium oxide (inert marker) , and fecal samples were collected with the modified Guelph method . A signi ficant, but minute apparent protein digestibility coefficient was observed for SBM (91%), when compared to FCP (89%). However, phosphorus was twice as available for FCP (85%) than SBM (42%) . For the comparative feeding trial, 900 channel catfish juveniles (~11.6 g initial weight) were equally distributed in 30 aquaria (110-L) working as a recirculating system and offered the experimental diets twice a day to apparent satiation for 60 days. The dietary treatments consisted of gradual replacement of SBM by FCP on an equal- nitrogen basis (0, 25, 50, 75, and 100%). At the end of the study, production performance parameters, viscerosomatic indices, blood, and whole-body proximate composition samples were collected. Fish were fed their assigned experimental diets for an additional three days and digesta samples were collected from the posterior segment of the intestine. Digesta samples were subjected to DNA extraction, and the 16S rRNA gene will be sequenced using an Illumina MiSeq to profile the intestinal microbiota. No differences were observed for hepatosomatic index, and survival, nor for whole-body protein, ash, and protein conversion efficiency. However, weight gain, feed efficiency, intraperitoneal fat, and whole-body lipid were significantly affected by the dietary treatments. The obtained results indicate that up to 50% of SBM can be replaced by FCP without causing any detrimental effects to juvenile catfish. After the feeding trial, the remaining fish were moved to a flow-through system and exposed to Edwardsiella ictaluri through immersion and mortality was monitored daily for 21 days. Interestingly, survival after the bacterial challenge gradually increased as the inclusion levels of FCP increased in the diets, with the 100% replacement treatment being significantly different than the basal diet (control) . In conclusion, FCP is a promising alternative protein ingredient with high protein digestibility , and it can replace half of the soybean meal in feed formulations for juvenile channel catfish, while enhancing disease resistance against E. ictaluri .