A 56-year-old male with a history of non-adherence to HIV anti-retroviral therapy (ART) presented with Elsberg syndrome -varicella reactivation causing fever, painful dermatomal rash, weakness of bilateral lower extremities, and urinary and bowel dysfunction. On the third day of hospitalization, the patient developed altered mental status. An investigation for encephalitis and myelitis revealed a CD4 count of 150 cells/uL, viral load of about 150,000 copies/mL, and MRI of the lumbar spine demonstrating thickening of the cauda equina. Cerebrospinal fluid (CSF) from lumbar puncture confirmed the presence of varicella-zoster virus (VZV). Treatment with acyclovir for 21 days was initiated. However, the patient developed a persistent fever. Evaluation for the source of the fever resulted in identification of anti-viral therapy as the cause. In conclusion, the present report provides a unique example of acyclovir-induced fever developed on treatment of Elsberg syndrome.