Strenuous endurance exercise increases inflammatory markers and acutely increases cardiovascular risk; however, statins may mitigate this response. We measured serum levels of p-selectin in 37 runners treated with statins and in 43 nonstatin treated controls running the 2011 Boston Marathon. Venous blood samples were obtained the day before (PRE) as well as within 1 hour after (FINISH) and 24 hours after (POST) the race. The increase in p-selectin immediately after exercise was lower in statin users (PRE to FINISH: 20.5 ± 19.4 ng/mL) than controls (PRE to FINISH: 30.9 ± 27.1 ng/mL; P < 0.001). The increase in p-selectin 24 hours after exercise was also lower in statin users (PRE to POST: 21.5 ± 26.6 ng/mL) than controls (PRE to POST: 29.3 ± 31.9 ng/mL; P < 0.001). Furthermore, LDL-C was positively correlated with p-selectin at FINISH and POST (P < 0.01 and P < 0.05, resp.), irrespective of drug treatment, suggesting that lower levels of LDL-C are associated with a reduced inflammatory response to exercise. We conclude that statins blunt the exercise-induced increase in p-selectin following a marathon and that the inflammatory response to a marathon varies directly with LDL-C levels.