Children with sickle cell anemia are at risk for brain injury. Physicians obtain brain magnetic resonance imaging (MRI) for clinical indications to determine if a patient has developed a brain injury. Controversy exists whether all children with sickle cell anemia should undergo MRI screening. This retrospective study evaluates the clinical and laboratory correlates for brain injury in 124 MRIs obtained for a variety of clinical indications. Seizure, sensory, or motor events were statistically associated with the highest risk for brain injury while less specific neurologic complaints of headache or poor school performance were not associated. Children with high systolic blood pressure, leukocytosis, and severe anemia demonstrate a higher probability for brain injury. These results indicate that brain MRI should be obtained on all children with seizure, sensory, or motor events. These data suggest that less specific neurologic symptoms should be screened if physical findings or abnormal lab or vital signs exist. © 2011 SAGE Publications.