Purpose: To examine how match performance parameters in trained footballers relate to skeletal muscle parameters, sprint ability and intermittent exercise performance. Methods: 19 male elite football players completed an experimental game with physical performance determined by video analysis and exercise capacity assessed by intermittent Yo-Yo IR1 and IR2 tests, and a repeated sprint test (RST). Muscle tissue was obtained for analysis of metabolic enzyme maximal activity and key muscle protein expression. Results: Total game distance, distance deficit from first to second half and high-intensity running in the final 15 min of the game were all correlated to the players’ Yo-Yo IR1 performance (r = 0.55–0.87) and beta-hydroxyacyl-CoA-dehydrogenase (HAD) maximal activity (r = 0.55–0.65). Furthermore, platelet/endothelial cell adhesion molecule-1 (PECAM1) protein expression was weakly (r = 0.46) correlated to total game distance. Peak 5-min game distance faster than 21 km h−1 was related to the Na+–K+ ATPase subunit (α1, α2, β1 and FXYD1) protein levels (r = 0.54–0.70), while Yo-Yo IR2 performance explained 40 % of the variance in high-intensity game distance. Total and 1-min peak sprint distance correlated to myosin heavy chain II/I ratio (MHCII/I ratio) and sarcoendoplasmic reticulum Ca2+ ATPase isoform-1 (SERCA1) protein (r = 0.56–0.86), while phosphofructokinase (PFK) maximal activity also correlated to total sprint distance (r = 0.46). Conclusion: The findings emphasize the complexity of parameters predicting physical football performance with Yo-Yo IR1 and HAD as the best predictors of total distance, while high expression of Na+–K+ ATPase proteins and the Yo-Yo IR2 test are better predictors of high-intensity performance. Finally, sprint performance relates to skeletal muscle fiber-type composition.