Abstract Funding Acknowledgements Type of funding sources: None. Objective To determine the clinical feasibility of novel serum biomarkers by comparing them with conventional serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM). Methods This study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured serum biomarker Neuron‑Specific Enolase (NSE), S-100B (S100 calcium-binding protein), Tau protein, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NFL), and Ubiquitin C-terminal hydrolase-L1 (UCH-L1) at 0, 24, 48, and 72 hours after return of spontaneous circulation (ROSC). Conventional biomarkers include NSE and S-100B. The primary outcome was good neurologic outcome at 6 months after OHCA. Results A total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes. As for the biomarker's AUC value measured immediately after ROSC, GFAP had the highest value (0.850), and among the values measured 24 hours after ROSC, S100B showed the highest value (0.901). The AUC values of biomarkers measured after 48 hours and 72 hours after ROSC, were the highest in NFL (0.921, 0.946). AUC values measured after 72 hours of ROSC showed higher values in novel biomarkers than in conventional biomarkers. Conclusion After 72 hours of ROSC, the Novel biomarkers showed a higher AUC value than the conventional biomarkers. Among them, NFL showed the highest AUC values than other biomarkers at 48 and 72 hours of ROSC.