The fhuCD system and its importance in Edwardsiella ictaluri virulence have not been studied yet. Previously, we constructed E. ictaluri ΔfhuCD mutants by in-frame deletion and allelic exchange. In the present study, the virulence of the EiΔfhuCD mutant was evaluated by immersion challenge using Specific Pathogen-Free channel catfish fingerlings and the ability of this mutant to protect the channel catfish against E. ictaluri was evaluated. Also, the ability of EiΔfhuCD mutant to grow in the presence of iron chelator 2,2’ Dipyridyl was assayed. The results indicated that little or no attenuation in EiΔfhuCD (40.00% mortality) was observed as compared to the parent E. ictaluri (%46.42). The channel catfish treated with EiΔfhuCD mutant showed high relative percent survival rates (average 94.72%) after re-challenge with E. ictaluri wild type. It was also found that the deletion of the E. ictaluri fhuCD operon did not affect E. ictaluri growth under iron-replete and iron-restricted conditions. Taken together, such data suggest that fhuCD operon is partial essential in E. ictaluri full virulence in channel catfish.