A 7 yr old castrated male Great Dane presented with a history of progressive myelopathy following the intramuscular injection of melarsomine dihydrochloride 8 wk previously. MRI revealed paraspinal and epidural abscesses at the 13th thoracic (T13) and first lumbar (L1) disc space. The dog's condition worsened despite medical management, necessitating surgical decompression. Surgical decompression resulted in rapid improvement of the patient's clinical signs. Histopathologic evaluation of the lesions revealed pyogranulomatous inflammation. Cultures of fluid and tissue within the lesions were negative for bacterial growth, and no infectious organisms were visualized histologically. Melarsomine-associated neurologic signs can be chronic and progressive in nature, presumably secondary to ongoing sterile inflammation that may result in spinal cord compression.