A 17-year-old female patient, known case of sickle cell anemia was admitted to our hospital with 10 days history of fever, vomiting, and epigastric pain. On examination, her temperature was 38°C. There was a vesicular type of rash below the nipple and over the left chest involving the back. She was diagnosed as herpes zoster and was started on acyclovir with good hydration and analgesia. Three days later, she developed weakness and decreased sensation of the right leg. On the fifth day, examination revealed power of 1/5 on the right leg, and 4/5 on the left leg, there was proximal and distal increased tone and brisk reflexes and up going toe on the right side with sensory level at T4-T6. An MRI of the thoracolumbar spine showed high signal intensity at T4-T6. The CSF analysis revealed positive polymerase chain reaction for varicella zoster. She was treated with intravenous (IV) dexamethasone 4 mg, 4 times per day. After 3 days she developed left leg weakness, urine incontinence, and power in the left leg was 3/5. Reflex plantar was up going bilaterally with sensory level at the nipple, T4-T6. She was then stared on IV methylprednisolone one gm for 3 days followed by a tapering dose of prednisolone 50 mg for 2 weeks, after a week of starting medication she was able to walk. This case of transverse myelitis is related to varicella zoster infection, with sickle cell anemia, and was successfully treated with high dose IV methylprednisolone, IV acyclovir, and physiotherapy.