Purpose Previous studies have suggested that extreme endurance exercise may induce cardiac microdamage that could lead to subsequent myocardial fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a cardiac biomarker for assessment of myocardial fibrosis, inflammation, and strain. We evaluated baseline and exercise-induced sST2 concentrations in a heterogeneous cohort of marathon runners to identify predictors for sST2 concentrations. Methods Ninety-two runners supplied demographic data, health status, physical activity levels, and marathon experience. Before (baseline) and immediately after (finish) the marathon, blood was collected for analysis of sST2 and cardiac troponin I (cTnI). Results Eighty-two participants (45 ± 8 yr, 79% male) finished the race in 227 ± 28 min at 92% (88%-94%) of their predicted maximum heart rate (exercise intensity). sST2 concentrations increased in all runners, from 34 (25-46) ng·mL -1 to 70 (53-87) ng·mL -1 (P < 0.001), and cTnI increased from 9 (5-21) ng·L -1 to 60 (34-102) ng·L -1 (P < 0.001). sST2 concentrations were higher in the fastest marathon runners. Sex and marathon personal best time were associated with baseline sST2 (R 2 = 0.27); baseline sST2, weight loss, and exercise intensity during marathon were associated with finish sST2 (R 2 = 0.54); baseline sST2, height, sex, and weekly training hours were associated with the exercise-induced increase in sST2 (R 2 = 0.47). We observed no association between sST2 and cTnI concentrations. Conclusion An exercise-induced increase in sST2 was observed in all marathon runners with sST2 concentrations exceeding cutoff values both at baseline (48%) and finish (94%). Faster runners had higher sST2 concentrations. Our data suggest complex variables determine sST2 concentrations in marathon runners.