Little is known about the correlation between the location and size of cerebral infarction in children and neuropsychologic deficits. We related lesion location and volume on magnetic resonance exams to neuropsychologic performance in 28 children with cerebral infarcts due to sickle cell disease. Seventeen healthy siblings served as a comparison group. Children with anterior cerebral infarcts (n = 7) showed deficits in attention and executive skills, whereas children with more widespread cerebral infarcts (n = 18) showed additional deficits in spatial skills. The volume of cerebral infarction was associated with spatial and language performance, but minimally related to performance in other cognitive domains. The location and volume of cerebral infarction are both important for defining the type and magnitude of cognitive sequelae in childhood stroke.