© 2016 Wiley Periodicals, Inc. Background: Patients with sickle cell disease (SCD) may experience many complications of the central nervous system (CNS) including stroke, silent cerebral infarcts, and neuropsychological deficits. Cranial epidural hematoma is a rare but potentially serious complication. Procedure: Case series of cranial epidural hematomas in children with SCD from three different institutions is considered, along with a literature review of cranial epidural hematomas in this population. Results: Seven children with SCD with cranial epidural hematomas were identified from three different institutions. All patients were male and the age at presentation ranged from 10 to 18 years. Two patients presented with headache (28.6%), while the rest had no neurologic symptoms at presentation. Four patients required urgent neurosurgical intervention (57.1%) and one patient died (14.3%). A literature review identified 18 additional cases of cranial epidural hematomas in children with SCD. Of these, treatment ranged from supportive care to neurosurgical intervention. Twelve patients completely recovered (66.7%), one patient had long-term cognitive impairment (5.6%), and four patients died (22.2%). Combined with our data, cranial epidural hematomas have a mortality rate of 20.0%. Conclusions: Although rare, cranial epidural hematoma can be fatal and should be considered in patients with acute neurological symptoms.