Patient: Male, 76-year-old Final Diagnosis: Powassan virus encephalitis Symptoms: Confusion • fever • respiratory distress Medication: Immunoglobulin • ceftriaxone Clinical Procedure: — Specialty: Infectious Diseases • General and Internal Medicine • Neurology Objective: Rare co-existance of disease or pathology Background: Powassan virus (POWV) is an emerging tick-borne flavivirus transmitted to humans by ticks. While infection is asymptomatic in some people, others develop life-threatening encephalitis with high mortality rates. Co-infection between POWV and Borrelia burgdorferi is rare despite the fact that both pathogens can be transmitted through the same tick vector, Ixodes scapularis. It is unclear if co-infection leads to more severe clinical presentation and worse outcome. Case Report: A 76-year-old Wisconsin man was admitted for meningoencephalitis complicated by hypoxemic and hyper-capnic respiratory failure requiring endotracheal intubation. The patient had no known tick bites but lived in a heavily wooded area. Extensive work-up for infectious, autoimmune, and paraneoplastic causes was positive for Borrelia burgdorferi and Powassan virus infection (POWV). Following treatment with ceftriaxone for neuroborreliosis and supportive care for POWV infection, the patient failed to improve. Intravenous immunoglobulins (IVIG) were started empirically, and the patient attained gradual neurological improvement and was successfully extubated. Conclusions: Treatment for POWV infection is supportive, and at this time there are no approved targeted antivirals for this disease. At this time, it remains unclear if co-infection with 2 pathogens leads to a more severe clinical presentation and higher mortality. In the absence of contraindications, IVIG might be beneficial to patients with POWV infection who are not improving with supportive care.