Purpose: Player monitoring in elite sport settings is becoming increasingly important. Questionnaire-based methods and biomarkers such as circulating, cell-free DNA (cfDNA) are suggested for load monitoring. cfDNA concentrations were shown to increase depending on total distance covered in football and were associated with overtraining in weight lifters. Thus, the objective of this study was to examine whether cfDNA is feasible as a monitoring tool in elite football players. Methods: Capillary blood samples from 22 male elite football players were collected over 4 mo of a regular season. Sampling was conducted the day before, 1 day after, or several days after regular-season games and/or training. In addition, each player filled in a visual analogue scale (VAS) questionnaire including the items “general perceived exertion,” “muscular fatigue,” and “mental fatigue.” Performance during training and games was tracked by the Catapult system and with the OPTA system, respectively. Results: cfDNA values were significantly elevated in players the day after regular-season games (1.4-fold; P = .0004) in line with the scores of the VAS. Both parameters showed significantly higher values during midweek-game weeks. cfDNA concentrations correlated with training data, and VAS was correlated with the tracking of the season games. However, cfDNA and VAS did not correlate with each other. Conclusions: cfDNA concentrations at rest and VAS scores are influenced by previous load in professional football players. Future studies will reveal whether cfDNA might serve as a practically applicable marker for player load in football players.