The effect of increased tissue injury in children with sickle cell disease and silent cerebral infarcts is not known. We determined the relationship between the extent of injury and IQ scores in children with silent cerebral infarcts. Participants were 27 children with sickle cell disease who had received magnetic resonance imaging (MRI). Children were divided into three groups: group 1, small lesion volume (n = 9, < 6.8 cm3); group 2, large lesion volume (n = 9; > 6.8 cm3); and group 3, no cerebral infarcts (n = 9). The Wechsler Full-Scale IQ was significantly lower for group 2 (mean = 76.1) when compared with group 1 (mean = 87.7) or group 3 (mean = 89.9). In children with silent cerebral infarcts, large tissue loss is associated with lower Wechsler Full-Scale IQ and small tissue loss is associated with no apparent change in IQ compared with children with no cerebral infarcts. The progressive accumulation of silent infarcts may lead to poorer intellectual functioning.