Objective: Headache is one of the most commonly reported and longest lasting symptoms that concussed athletes report, yet the etiology of headache symptoms following concussion is not entirely clear. The purpose of this study was to determine whether the e4 allele of the apolipoprotein E (APOE) gene influences the presence and severity of post-concussion headache. It was hypothesized that the e4 allele would be associated with more severe headache symptoms following concussion. Method: Participants were comprised of 45 concussed athletes (82.2% male) who participated in a clinically-based sports concussion management program. All athletes underwent neuropsychological testing, which included completion of the Post-Concussion Symptom Scale (PCSS), within three months after sustaining a concussion (71.1% were evaluated within one week). DNA was collected via buccal samples, and was analyzed to determine APOE genotype. Results: After dividing the sample into e4+ (n = 16) and e4− (n = 29) groups, no significant differences were found between the groups on demographic and injury severity characteristics. A Mann-Whitney U test showed significant differences in headache severity between the groups, with e4+ athletes endorsing more severe headaches (p = .023). Finally, using logistic regression, the e4 allele significantly predicted the presence of post-concussion headache, χ2(1, N = 45) = 4.85, p = .028, and accounted for 14% of the variance. Conclusion: These findings show that when compared to e4− athletes, e4+ athletes are more likely to (1) endorse post-concussion headache and (2) report more severe headache symptoms following concussion. Results suggest that those with the e4 genotype may be at a higher risk for experiencing headache-related difficulties following concussion.