Aim: The primary purpose of this study was to investigate the relationship between the pre-game to post-game changes in creatine kinase concentration (Δ[CK]) and impact-related game statistics in elite rugby union players. Methods: Twenty-three elite male rugby union players each provided interstitial fluid samples obtained via electrosonophoresis (ESoP) 210 min before and within a maximum time of 30 min after up to five rugby union games. Specific game statistics that were deemed to be important in determining the relationship between impact and [CK] were obtained from AnalyRugby software for each individual player. Regression equations to predict Δ[CK] from game statistics were created using a backwards random-effects maximum likelihood regression. Results: The Δ[CK] (mean (SD)) from pre-game to post-game was 926.8 (204.2) IU. Game time and time defending were significantly correlated to Δ[CK] in both the forwards and backs. The predicted Δ[CK] (mean (95% confidence limit)) was 1439.8 (204.9) IU for the forwards and 545.3 (78.0) IU for the backs and was significantly correlated with the actual Δ[CK] (r = 0.69 and r = 0.74). Conclusions: CK increased from pre-game to post-game in a position-specific manner. A large proportion of the Δ[CK] can be explained by physical impact and thus can be predicted using a prescribed number of game statistics. As the Δ[CK] is an indicator of muscle damage, the prediction of Δ[CK] provides a theoretical basis for recovery strategies and adjustment of subsequent training sessions after rugby union games.