Encephalopathy is a disturbance in neurologic function. It is commonly attributed to infectious and inflammatory etiologies but encompasses a wide differential. Hypereosinophilic syndrome (HES) is a rare cause of encephalopathy that is associated with underlying infection or malignancy. We present a pediatric patient who experienced several days of worsening encephalopathy and neurological deterioration associated with influenza B infection and hypereosinophilia. A thorough workup ultimately revealed a diagnosis of HES secondary to B cell acute lymphoblastic leukemia (B-ALL). This case exemplifies the importance of maintaining a broad approach to the diagnostic evaluation, treatment, and management of encephalopathy.