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Purpose Exposure to repetitive head impacts sustained during routine sports participation may result in elevated levels of brain-derived biomarkers (BDM) glial fibrillar acidic protein (GFAP), NFL, total tau and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) independent of concussion occurrence. However, the extent to which sport career duration and sex influence BDM remains unclear. This cross-sectional study examined whether biological sex and exposure-related variables, including age of first exposure to contact sports and time since most recent concussion, were associated with preseason serum concentrations of four brain-derived biomarkers in healthy contact and collision sport athletes.Methods Male and female collegiate athletes (n=700) participating in contact and collision sports were recruited from six Concussion Assessment, Research and Education (CARE) Consortium sites. Non-fasting venous blood samples were collected during preseason testing, and serum concentrations of GFAP, NFL, UCH-L1 and total tau were quantified. General linear models were used to examine whether biomarker concentrations differed by sex, with sport included as a covariate to account for differences in head impact exposure profiles, age of first exposure (AFE) to contact sports and time since most recent concussion. Separate univariate regressions were conducted within football athletes.Results Sex significantly predicted GFAP (p<0.001, η²=0.123) and NFL (p=0.029, η² =0.042) concentrations, with females exhibiting higher serum levels than males. Neither sport, AFE nor time since concussion significantly influenced biomarker concentrations. No significant predictors were identified for UCH-L1 or total tau. In the football-specific analysis, AFE and time since concussion were not associated with biomarker levels.Conclusion Collegiate females participating in contact and collision sports have significantly higher GFAP and NFL serum concentrations than age-matched and sport-matched males, independent of sport, AFE and time since concussion. These findings may contribute to understanding sex-based biological sensitivity to head impact exposure and support the development of biomarker-informed monitoring strategies in athletes.