Abstract:[Background] A fish disease occurred in a snakehead farm in Yangzhou, Jiangsu Province, causes great economic losses. [Objective] To determine the etiology and screen out sensitive drugs for the control of snakehead-related diseases. [Methods] The pathogenic bacteria were isolated from the sick snakeheads, and the isolates were identified in terms of morphology, physiological and biochemical characteristics, 16S rRNA gene and gyrB sequences and specific PCR assays, while their pathogenicity was analyzed by artificial infection tests and antimicrobial sensitivity was tested by paper diffusion method. [Results] A dominant strain SHL isolated from the sick snakeheads was identified as Edwardsiella piscicida, by its morphological characteristics, physicochemical properties, 16S rRNA gene and gyrB sequences, specific PCR results, and further artificial infection tests confirmed its strong pathogenicity to snakeheads with an LD50 of 1.6×105 CFU/g with similar symptoms to natural disease. The drug sensitivity test results showed that the strain was highly sensitive to 28 antibacterial drugs such as penicillin, chloramphenicol and tetracycline, moderately sensitive to erythromycin, and resistant to 6 drugs such as oxacillin, clarithromycin and vancomycin. [Conclusion] Edwardsiella piscicida is the pathogen causing the ulceration and death of snakeheads (Channa argus) cultured in Yangzhou, Jiangsu province. It is the first time that Edwardsiella piscicida was detected from freshwater fish in China. The results demonstrated that the infection spectrum of Edwardsiella piscicida is expanding, which needs to be paid more attention in the field of aquaculture. In aquaculture practice, we can treat the disease with the appropriate national standard fishery drugs according to the results of the drug sensitivity test.