Progressive myelopathy in immunocompromised patients presents a broad differential diagnosis and requires careful localization, imaging interpretation, and correlation with clinical context. A 66-year-old man with human immunodeficiency virus and diabetes mellitus developed vertigo, followed by asymmetric limb weakness beginning in the right leg and later progressing to the left leg, trunk, and upper extremities; gait imbalance with falls; paresthesias; and urinary urgency approximately 3 months after restarting antiretroviral therapy and 4 weeks after receiving a COVID-19 booster shot. Neurologic examination revealed mild symmetric quadriparesis, brisk reflexes, and impaired proprioception in the lower limbs. CSF analysis demonstrated elevated protein, oligoclonal bands, and an elevated immunoglobulin G index. Magnetic resonance imaging demonstrated longitudinally extensive tract-specific spinal cord abnormalities, which resolved spontaneously after several months without immunotherapy. This report illustrates the stepwise approach to myelopathy in immunocompromised patients, emphasizing the differential diagnosis for tract-specific imaging findings, clinical localization, and the role of immune reconstitution in neurologic disease.