Since the first-reported case of Severe Acute Respiratory Distress Syndrome-Coronavirus 2 in December 2019, COVID-19 has caused a global pandemic associated with significant morbidity and mortality. After a year of advances in vaccine research and development, three vaccines for the prevention of COVID-19 (manufactured by Pfizer, Moderna and Johnson & Johnson's Janssen Biotech) are approved for use in the USA. We report the first case of Guillain-Barre Syndrome after receiving the second dose of the Pfizer COVID-19 vaccine, in a 42-year-old woman presenting with progressive ascending weakness and paresthesias. Diagnostic workup demonstrated cytoalbuminologic dissociation on cerebrospinal fluid analysis with confirmatory evidence of early demyelinating electrodiagnostic features on nerve conduction study and an extensive serological workup being negative for other viral or autoimmune disease triggers. Management included administration of intravenous immunoglobulin (total of 2 gm/kg), with frequent monitoring of forced vital capacity and negative inspiratory force. A longitudinal risk profile of neurologic complications caused from COVID-19 vaccines remains limited, and prompt recognition of potential neurological complications from the COVID-19 vaccine is of interest to public health.