Silent cerebral infarctions have been shown to cause major morbidity in children with sickle cell disease, suggesting that silent infarctions are not as "silent" as once thought. The current definition of silent infarction includes signal changes on magnetic resonance imaging, the absence of overt abnormalities on neurologic examination, and no history of focal neurologic event. Using a decision tree algorithm, we identified a cognitive profile distinguishing children with (n=16) and without (n=49) silent infarctions. The best model combined learning slope from the California Verbal Learning Test-Children's Version and Block Design from the Wechsler Abbreviated Scale of Intelligence. Accuracy was 75%, with 75% sensitivity and 76% specificity. Administration of a brief cognitive battery may be the most feasible approach to screen for silent infarctions in children with sickle cell disease.