Cerebral palsy is attributed to non-progressive disturbances in the developing fetal or infant brain. The APOE ε4 allele has been associated with poor outcome after brain injury in adults but may be protective among very young children. We conducted this study to explore the hypothesis that the APOE ε4 is associated with lowered severity of cerebral palsy. 158 individuals with CP and their parents were genotyped for APOE. Mean age was 9.1 years; 54% were males. 61% were preterm at birth; 34% less than 30 weeks gestation. 30% of the CP subjects had at least one ε4 allele. There was a trend towards significance for subjects with at least one ε4 allele assigned to the low severity group (p = 0.11). The greater number of ε4 alleles, the more likely an individual was in the low severity CP group (p = 0.12). Individuals with brain injury in the perinatal period were almost 5 times more likely to be in the low severity group (p < 0.01). Family analysis via the TDT supported a protective effect of APOE ε4. Further study is needed to confirm that, in contrast to adults, the APOE ε4 allele appears to confer protection and/or facilitate recovery after brain injury in the fetus or newborn, particularly when that injury occurs around term.