We compared the cut-off and prognostic value of serum neuron-specific enolase (NSE) between groups with and without severe blood–brain barrier (BBB) disruption to reveal that a cause of various serum NSE cut-off value for neurological prognosis is severe BBB disruption in out-of-hospital cardiac arrest (OHCA) patients underwent target temperature management (TTM). Here, ENO2 is linked to cardiac arrest.