Technical Abstract: Edwardsiella ictaluri and Flavobacterium columnare are two bacterial pathogens that impact the channel catfish Ictalurus punctatus aquaculture. Some progress has been made at the USDA-ARS Catfish Genetics Research Unit in selectively breeding for resistance to E. ictaluri; however, the susceptibility of these families to F. columnare is not known. The objectives of this study were to obtain baseline information on the susceptibilities of channel catfish families, maintained as part of the selective breeding program, to E. ictaluri and F. columnare and to determine if spleen index and plasma levels of mannose-binding lectin (MBL) are predictive indicators of susceptibility to these pathogens. Four families of channel catfish were used: family A was randomly chosen from spawns of catfish that had not been selectively bred for resistance; families B, C, and D were families obtained following selection for resistance to E. ictaluri. All four families were challenged by immersion with both bacterial pathogens and the spleen index and plasma MBL levels of unchallenged fish were determined. Mean cumulative percent mortality (CPM) of the families following E. ictaluri challenge ranged from 4 to 33%. Families A and B were more susceptible to F. columnare (mean CPM of three independent challenges, 95 and 93%)than families C and D (45 and 48%), demonstrating that there is genetic variation in resistance to F. columnare. Spleen index and MBL levels were not significantly different, suggesting that these metrics are not predictive indicators of susceptibility to F. columnare or E. ictaluri in the four families that were tested. An interesting observation was the two families that exhibited the highest CPM following the F. columnare challenges had the lowest CPM following E. ictaluri challenge. Further research on larger numbers of families is needed to determine if there is any genetic correlation between resistance to E. ictaluri and F. columnare.