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Climate change will likely promote the emergence of the mesophilic bacteria Photobacterium damselae subsp. damselae as a pathogen affecting global economic marine fish farming. In this study, we identified links between P. damselae subsp. damselae and skin ulcerations in commercially farmed half-smooth tongue sole (Cynoglossus semilaevis) in the Bohai Bay area. Nearly circular ulcerations appeared on the pigmented side of the diseased fish and were caused by damage to the epidermis, dermis, and muscular layers, with significant congestion found in the brain, liver, and intestine accompanied by significant pathological changes. Physiological and biochemical characterization and 16S rRNA gene sequencing identified six kinds of bacteria isolated from diseased fish, with artificial-infection testing and histopathologic analysis revealing P. damselae subsp. damselae as the cause of death and the variable clinical symptoms (abdominal swelling and skin ulcers) observed following injection with different concentrations of bacterial suspension (similar to 10(4)-10(6) CFU mL(-1)). Additionally, histological analysis showed that the pathological changes induced by the bacterial suspensions were similar to those found in naturally diseased fish; however, the degree of damage differed according to time after infection. Moreover, antimicrobial-susceptibility testing showed that P. damselae subsp. damselae exhibited different degrees of resistance to 11 of 13 types of antibacterial drugs but strong susceptibility to chloramphenicols, suggesting their efficacy for first-line treatment of diseased fish.