Creatine kinase (CK) is an enzyme catalyzing energy reaction in muscle cells and has proven to modify cardiovascular risks. The influence of skeletal muscle activity on CK concentrations is a potential study confounder but is mainly reported in connection with sport activities. This study investigated the association between leisure physical exercise and CK and estimated the effect of physical exercise on the CK values. CK and leisure physical exercise defined as intensity, frequency, and duration subsets were measured in the population-based Tromsø study. Comparisons of CK at different exercise levels, multivariate analyses, and relative differences in CK between "never exercise" and "heavy exercise" (moderate or hard exercise =2 hours per week) subgroups were analyzed age- and sex-stratified in 12 796 men and women. CK increased significantly with higher levels of physical exercise intensity and frequency in both sexes analyzed by ANOVA. In a multivariate analysis, CK was independently associated with heavy exercise after adjusting for age, BMI, and blood pressure; OR 9.38 (95% CI 5.32-16.53), P