Guillain-Barré syndrome (GBS) and GBS-like syndromes secondary to West Nile virus (WNV) are rare and poorly characterized. GBS is an immune-mediated disease that affects peripheral nerves, classically in a symmetrical and ascending pattern. It is generally associated with infectious microbes, but not classically with WNV. WNV, although a relatively new pathogen in the United States, has become a leading mosquito-borne viral infection in the country. We present a case of a patient who came to the hospital in Delaware, USA, with fever and confusion that rapidly progressed to worsening encephalopathy and paralysis requiring intubation and vasopressor support. This case emphasizes the need to include GBS or GBS-like syndromes on the differential in patients with encephalopathy and neurological changes, particularly in the setting of an increasing incidence of WNV infection in the United States.