Guillain-Barre syndrome (GBS) and transverse myelitis (TM) are both neuro-inflammatory disorders that are attributed to dysfunctions of the peripheral nervous system and spinal cord, respectively. The two conditions involve immune-mediated destruction and inflammation of the nervous system and may present clinically as a weakness in the muscles, loss of normal sensations, and even paralysis of the body or extremities. Although the incidence of GBS and TM is quite rare, there have been reports of the two diseases developing in patients, either independently or concurrently, following COVID-19 vaccinations. In this case report, we present a patient (male) who lost functions and sensations in his lower extremities 60 days after he received the COVID-19 booster vaccine. The patient’s blood work was unremarkable. Magnetic resonance imaging (MRI) of his thoracic spine and an electromyography study revealed evidence of nerve demyelination, which supports the diagnosis of GBS/TM overlap syndrome. He was ultimately treated with intravenous immunoglobulins (IVIGs) and gained back functions in his lower extremities.