Background: Near-infrared spectroscopy (NIRS) provides regional tissue oxygenation (rSO 2 ) even in pulseless states, such as out-of-hospital cardiac arrest (OHCA). Brain rSO 2 seems to be important predictor of return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). Aim of our study was to explore feasibility for monitoring and detecting changes of skeletal muscle rSO 2 during resuscitation., Methods: Skeletal muscle and brain rSO 2 were measured by NIRS (SenSmart Model X-100, Nonin, USA) during CPR in adult patient with OHCA. Start (basal) rSO 2 , maximal during CPR (maximal) and difference between maximal-minimal rSO 2 (delta-rSO 2 ), were recorded. Patients were divided into ROSC and NO-ROSC group., Results: 20 patients [age: 66.0ys (60.5-79.5), 65% male] with OHCA [50% witnessed, 70% BLS, time to ALS 13.5 min (11.0-19.0)] were finally analyzed. ROSC was confirmed in 5 (25%) patients. Basal and maximal skeletal muscle rSO 2 were higher in ROSC compared to NO-ROSC group [49.0% (39.7-53.7) vs. 15.0% (12.0-25.2), P = 0.006; 76.0% (52.7-80.5) vs. 34.0% (18.0-49.5), P = 0.005, respectively]. There was non-linear cubic relationship between time of collapse and basal skeletal muscle rSO 2 in witnessed OHCA and without BLS (F-ratio = 9.7713, P = 0.0261). There was correlation between maximal skeletal muscle and brain rSO 2 (n = 18, rho: 0.578, P = 0.0121)., Conclusions: Recording of skeletal muscle rSO 2 during CPR in patients with OHCA is feasible. Basal and maximal skeletal muscle rSO 2 were higher in ROSC compared to NO-ROSC group. Clinical trial registration number ClinicalTrials.gov, NCT04058925, registered on: 16th August 2019. URL of trial registry record: https://www., Clinicaltrials: gov/ct2/show/NCT04058925?titles=Tissue+Oxygenation+During+Cardiopulmonary+Resuscitation+as+a+Predictor+of+Return+of+Spontaneous+Circulation&draw=2&rank=1 ., (© 2023. BioMed Central Ltd., part of Springer Nature.)