Posterior reversible encephalopathy syndrome is an acute or subacute neurological disorder with variable clinical manifestations including encephalopathy, headache, seizures, visual disturbance, and focal neurologic deficits. Neuroimaging often shows frequently reversible vasogenic edema that predominantly involves the subcortical parieto-occipital lobes. Posterior reversible encephalopathy syndrome has been associated with hypertension and reported in patients with many conditions including eclampsia/pre-eclampsia and immunosuppressive therapy. Recently, posterior reversible encephalopathy syndrome is recognized to occur in association with severe infections such as complicated appendicitis. Here, we describe a case of 11-year-old male admitted for complicated appendicitis and severe sepsis. He developed seizures and had an altered mental status 10 days into his hospitalization with brain magnetic resonance imaging findings consistent with posterior reversible encephalopathy syndrome. We review the pediatric literature and discuss the pathogenesis of posterior reversible encephalopathy syndrome in association with an infection. We highlight the importance of recognizing this syndrome as a possible cause for acute neurological deterioration in children with severe infections.