An 11-year-old female African Clawed Frog presented to Cornell's Exotics Service for edema and regurgitation and 6 months later, cutaneous ulcerations and inappetence. Despite treatment with antibiotics, antifungals, anti-inflammatories, and electrolyte soaks, the patient died approximately 1 month after the development of ulcerations. The presumptive diagnosis was bacterial septicemia with initial improvement based on clinical signs and initial response to antibiotic therapy, but several common differentials for edema and skin lesions in frogs will be discussed, including ranavirus infection. Other topics discussed in this report include African Clawed Frog natural history, husbandry, cytology, and treatment and diagnostic options for presumptive bacterial septicemia.