Cholesterol is an essential substance to maintain cell membranes. Low levels of total cholesterol (TC) are associated with poor prognosis in critically ill patients. Cardiac arrest-induced whole-body ischemia and reperfusion injury cause a sepsis-like syndrome. The Cholesterol level in post-cardiac arrest patients may indicate the degree of endotoxemia or inflammation caused by ischemic and reperfusion injury. We aimed to investigate the association of TC levels with neurologic outcome of out-of-hospital cardiac arrest (OHCA) survivors who underwent target temperature management (TTM). This was a retrospective single-center observational study from May 2018 to April 2021 on a cohort of 106 patients. TC levels were determined in samples obtained immediately and at 24, 48, and 72 hours after the return of spontaneous circulation (ROSC). The primary outcome was poor neurologic outcome at 3 months after ROSC. Poor neurologic outcome was defined by cerebral performance categories 3 to 5. Sixty patients had a poor neurologic outcome. TC levels were significantly lower in the poor neurologic outcome group at each time point. The TC levels for predicting poor neurologic outcome had a sensitivity of 80.8%, with 67.6% specificity at 48 hours (TC 48 ) after ROSC. The areas under the curve value of TC 48 was 0.771 (0.670-0.853), with a cutoff value of 114 mg/dL. TC level at 48 hours after ROSC was a helpful marker for the 3-month poor neurologic outcome. This might be an easily accessible predictive marker of neurologic outcome in OHCA survivors treated with TTM.Abbreviations: AUROC = area under the ROC curve, CI = confidence interval, CPC = cerebral performance category, CPR = cardiopulmonary resuscitation, IL-6 = interleukin-6, NSE = neuron-specific enolase, OHCA = out-of-hospital cardiac arrest, PCAS = post-cardiac arrest syndrome, ROC = receiver operating characteristic, ROSC = return of spontaneous circulation, TC = total cholesterol, TTM = target temperature management.