In fish possessing a swim bladder, buoyancy depends on the hydrostatic maintance of gas within the vesicular space. Abnormalities of this structure can cause changes in buoyancy. Freshwater fish within the family Cyprinidae contain two compartments within the swim bladder with a pneumatic duct that connects the gastrointestinal tract to the swim bladder. This connection to the GI tract creates a predisposition to microbial infection within the duct or ascending into the bladder itself. A six-year-old female Carassius auratus and a two-year-old female Cyprinus rubrofuscus presented with negative buoyancy and inversion within the water column. Bloodwork, advanced imaging (computed tomography and ultrasonography), and next-generation microbial sequencing demonstrated vesicular effusion (swim bladder fluid accumulation), suspected aerocystitis, and bacterial overgrowth within the swim bladder. For the koi fish, Shewanella xiamenensis was identified as the most prominent microbial organism within the vesicular effusion. The fish was treated with parenteral Ceftazidime. The koi remained asymptomatic for 2 years post-treatment and was eventually euthanized after a relapse of buoyancy issues. On postmortem examination, there were numerous yellow to white, round to irregular nodules throughout the wall of the stomach. Histopathologic examination revealed severe fibrinous coelomitis with severe necrotizing gastritis, mild chronic oophoritis and enteritis, and myeloid renal hyperplasia. For the goldfish, Stenotrophomonas maltophilia was identified as the only microbial organism within the vesicular effusion. Treatment consisted of parenteral Ceftazidime and Robenacoxib. With this treatment, the goldfish’s symptoms resolved.