An 18-year-old man presented with 5-days of a lower extremity rash, sore throat, rapidly progressive bilateral facial numbness and paresthesias in his distal extremities. His neurological examination acutely deteriorated to include moderate bilateral facial weakness in a lower motor neuron pattern, mild flaccid dysarthria, mild bilateral interossei weakness, and diffuse hyporeflexia. In addition to neurological examination, EMG results of acute demyelinating polyradiculoneuropathy were suggestive of Guillain-Barre Syndrome (GBS). Infectious laboratory testing demonstrated acute infection of Epstein-Barr Virus (EBV) with relatively low EBV DNA quantitative values. The patient subsequently developed fever and cervical lymphadenopathy during his hospital course. Contrasting typical GBS, which presents weeks after an acute infection, the patient's presenting symptom of EBV infection was GBS. GBS as a presenting symptom of EBV has not previously been described. This case may represent a unique mechanism for the pathogenesis of GBS in acute infections as opposed to the traditional post-infectious antibody-mediated process.