The purpose of this exploratory study was to examine interactive relationships between a common brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) and biological sex on cognitive functioning in a sample of healthy adolescent athletes. Participants included 82 student athletes (age: M = 12.85 years, SD = 1.13) who were involved in a clinically-based sports-concussion management program. Athletes completed the ImPACT computerized battery at baseline and provided buccal samples for determination of their BDNF genotype. Two-way ANOVAs were used to evaluate the effect of BDNF genotype (Met+ vs. Met-) and sex (male vs. female) on cognitive functioning (subgroup n’s: Female/Met+ = 12, Female/Met- = 26, Male/Met+ = 12, Male/Met- = 32). ANOVAs revealed non-significant main effects for both BDNF genotype and sex across all four cognitive composites. However, there was a significant BDNF genotype by sex interaction for the visual-motor speed composite (p = .015; etap(2) = .073), such that female Met carriers demonstrated better performance than male Met carriers. In contrast, no differences were found on visual-motor speed performance between females and males without a Met allele. Although these results will need to be replicated using larger samples, our preliminary findings lend support to the view that the Met allele may be somewhat neuroprotective in healthy adolescent females.