PurposeUreaplasma speciesare associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media withUreaplasma parvumin a patient with granulomatosis with polyangiitis (GPA).MethodsImaging and laboratory findings, treatment decisions, and outcome of this case are explicated.ResultsA young adult with GPA presented with progredient earache after ambulant diagnosis of otitis media. Despite different courses of broad-spectrum antibiotic therapy, she developed meningoencephalitis due to mastoiditis following temporal abscess formation. Mastoidectomy and neurosurgical abscess removal were performed. Standard cultures of cerebrospinal fluid, blood and intracranial abscess material, as well as polymerase chain reaction (PCR) for common bacterial and viral meningitis pathogens remained negative. Only eubacterial PCR of intracranial abscess material returned positive forUreaplasma parvum.The patient finally improved under antibiotic therapy with moxifloxacin and doxycycline.ConclusionUreaplasma speciesare rare causative pathogens in immunocompromised patients. They should be considered in patients with humoral immunodeficiencies with culture-negative infections failing standard therapy. Eubacterial PCR should be performed in early states of infection in these patients for immediate diagnosis and initiation of appropriate treatment to prevent adverse outcomes.