The aim of this study was to investigate the effect of pre-exercise whole-body cryotherapy (WBC) on muscle damage indicators following eccentric treadmill exercise in young women. Twenty-seven participants underwent two 1-h downhill treadmill runs, replicating 60% of their maximal oxygen uptake, with a 4-week intermission for recovery and treatment application. In this intermission, one group underwent 20 sessions of WBC, delivered five times a week at -120°C for 3 min each, while the comparison group received no such treatment. Markers of muscle injury-serum myoglobin concentration, creatine kinase and lactate dehydrogenase activity and also uric acid, and cell-free DNA concentration-were measured before and after downhill runs. The study observed a notable reduction in post-exercise myoglobin and CK levels in the WBC group after the second running session. The results suggest that WBC can have a protective effects against muscle damage resulting from eccentric exercise.