ABSTRACT: Gas-bubble disease (GBD)—a non-infectious disease in aquatic organisms caused by supersaturated levels of total dissolved gases (oxygen and nitrogen) in water—is well-known in various species, including fish and amphibians, but has not been reported in giant salamanders. Macroscopic and histopathological examinations of two mature Andrias spp. (kept with 293 fish in an aquarium) were performed to characterize the GBD pathology. Bubbles developed on the body surfaces of the salamanders and fish, with erythema specifically noted in the salamanders. Within 3 days of the bubbles appearing, two salamanders and more than 270 fish had died. On days 1 and 2, dissolved oxygen levels were 75.5 and 86.9%, respectively, while dissolved nitrogen gas levels were 90.6 and 103.1%, respectively. The two salamanders exhibited identical lesions characterized by erythema, congestion, and numerous bubbles in the major veins of the body cavity. Histopathologically, congestion and gas embolism-like dilatations were observed in the small vessels and capillaries. These lesions were found in the parenchymal and gastrointestinal organs, skin, eyeballs, and surrounding stromal tissue. Based on these findings and that GBD occurs at dissolved nitrogen gas and oxygen levels above 120 and 200%, respectively, the salamanders were diagnosed with nitrogen-GBD. The exact etiology of this disease remains unconfirmed but likely involves circulatory system dysfunction within the aquarium environment, highlighting the importance of routine inspections and maintenance of equipment.