Objectives: This study investigated chronic changes in cell free DNA (cf-DNA) throughout a collegiate soccer season. The relationship between cf-DNA, C-reactive protein (CRP), creatine kinase (CK), testosterone (T), cortisol (C), testosterone-cortisol ratio (T:C), body mass and body composition were also examined. Design: Longitudinal study design with repeated measures and group comparisons.Methods: Twenty three NCAA Division I male soccer players were divided into two groups. Starters were placed in Group 1 (G1) and non-starters were placed in Group 2 (G2). cf-DNA, CRP, CK, T, C, T:C, body mass and body composition were taken three times, corresponding to pre-season, approximately mid-season and immediately after the concluding the season.Results: In G1, cf-DNA, CRP, CK, cf-DNA %∆, CRP %∆ and, CK %∆ were all statistically higher at T2 and T3 than T1. In G2, CRP %∆ was statistically higher at T2 than T1. In G2, cf-DNA %∆, CRP %∆ and CK %∆ were higher at T2 and T3 than T1.Conclusions: This suggests that cf-DNA may be a useful marker that can reflect accumulated soccer training and competitive stressors.