In April 2011, there was an outbreak of an infectious disease in southern catfish, Silurus soldatovi meridionalis, (Chen) (15–20 g) in Sichuan Province, China. Two isolates, LW101 and LW102, were isolated from kidney and liver of the sick fish on brain-heart infusion (BHI) agar and were considered to be the cause of this disease based on experimental challenges. The morphological and physiological characteristics as well as the biochemical tests of the two isolates were the same and similar to Edwardsiella ictaluri. Furthermore, the sequencing of the 16S rRNA gene and the gryB gene revealed that the isolates were highly homogeneous with E. ictaluri. On the basis of the phenotypic characteristics and phylogenetic analysis of these genes, both isolates were identified as E. ictaluri. Susceptibility of the isolates to 22 antibiotics was tested using the disc diffusion method. Both isolates showed a similar antibiotic susceptibility, which was characterized by resistance to acetylspiramycin, ampicillin, clarithromycin, penicillin, oxytetracycline, and sinomin (SMZ/TMP); the strains were susceptible to amikacin, chloramphenicol, florfenicol, roxithromycin, ciprofloxacin, norfloxacin, doxycycline, and tenemycin. To our knowledge, this is the first report of E. ictaluri infection in southern catfish.