Background: Rugby union players can take several days to fully recover from competition. Muscle damage induced during the match has a major role in player recovery; however the specific characteristics of match play that predict post-match muscle damage remains unclear. We examined the relationships between a marker of muscle damage and performance characteristics associated with physical contacts and high-speed movement in professional rugby union players. Methods: Twenty-eight professional rugby union players (15 forwards, 13 backs) participated in this study. Data were obtained from 4 European Cup games, with blood samples collected 2 h pre, and 16 and 40 h post-match, and were subsequently analysed for creatine kinase (CK). Relationships between changes in CK concentrations and number of physical contacts and high-speed running markers, derived from performance analysis and global positioning system (GPS) data, were assessed. Results: Moderate and moderate-large effect-size correlations were identified between contact statistics from performance analysis and changes in CK at 16 and 40 h post-match in forwards and backs, respectively (e.g. backs; total impacts vs. ΔCK (r = 0.638, p < 0.01) and Δ% CK (r = 0.454, p < 0.05) 40 h post-match). Furthermore, moderate effect-size correlations were found between measures of high-speed running and sprinting, and changes in CK at 16 and 40 h post-match within the backs (e.g. high-speed running distance vs. ΔCK (r = 0.434, p = 0.056) and Δ% CK (r = 0.437, p = 0.054) 40 hrs post-match). Conclusions: Our data demonstrate that muscle damage induced by professional rugby union match play is to some extent predicted by the number of physical contacts induced during performance. Furthermore, we show for the first time that muscle damage in backs players is predicted by high-speed running measures derived from GPS. These data increase the understanding of the causes of muscle damage in rugby union; performance markers could potentially be used to tailor individual recovery strategies and subsequent training following rugby union competition.