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Cystitis is a frequent, often chronic and recurrent disease in guinea pigs (Cavia porcellus). This report describes a case of a 2-year-old, entire, female Abyssinian guinea pig with fatal cystitis. The animal was presented with progressive chronic cystitis and had previously been treated with several antibiotics and analgesics. Radiographs demonstrated a mineral-dense opacity in the urinary bladder, and urinalysis revealed numerous leukocytes. The animal received subcutaneous fluid boluses and a change of antibiotic treatment. The general condition deteriorated, and the animal died acutely 1 day after being admitted to the hospital. Pathology revealed severe, chronic-active, multifocal, purulent to fibrinous, haemorrhagic cystitis. A bacteriological examination of the urinary bladder wall and urinary bladder contents revealed Facklamia sourekii, Corynebacterium renale and Enterococcus casseliflavus. Myocarditis and steatitis were also noted, supporting sepsis secondary to cystitis as the cause of death.