Abstract Funding Acknowledgements Type of funding sources: None. Background Patients who are successfully resuscitated from out-of-hospital cardiac arrest (OHCA) and admitted to the hospital in a comatose stage are in high risk for anoxic brain injury. Multimodal approach for neuroprognostication include measurement of neuron-specific enolase (NSE) as a biomarker for neurological injury. NSE has been intensively studied over the past years and has shown a valid predictive value for neurological outcome. However, there has been no clinical studies comparing NSE analyzed on plasma and serum samples. Purpose To compare NSE at 48 hours obtained from both in serum and plasma samples, and to investigate the performance of both these measuring techniques in predicting all-cause mortality at 365-days among patients resuscitated from out-of-hospital cardiac arrest. Methods This is a post-hoc sub study of the BOX trial in which resuscitated OHCA patients admitted to the hospital in comatose stage were included. NSE was measured 48 hours after admission, both in serum samples used for clinical analysis with no freeze-thaw cycle (NSE-Serum), and plasma samples from biobank (NSE-Plasma). The comparison of NSE-Serum and NSE-Plasma was performed by Spearmans correlation. The area under the receiver operating characteristics curve (AUROC) for predicting all-cause mortality at 365-days for both NSE-Serum and NSE-Plasma were determined. Results 369 patients had NSE values from both serum and plasma at 48 hours available for comparison. In these patients the NSE-Serum was median 21.2 µg/L (IQR 15.7 - 45.5), NSE-Plasma was median 19.3 µg (IQR 11.3 - 40.9), and mortality at 365-days was 32.5%. The correlation between NSE-Serum and NSE-Plasma was r=0.63 P<0.001. AUROC for NSE-Serum and NSE-Plasma were 0.94 and 0.83 respectively (FIGURE), and the differences in AUROC was -0.10 (95% confidence limits: -0.14 to -0.06), p<0.001. Conclusion In this sub study, we found moderate correlation between serum NSE values and plasma NSE values. Moreover, both measuring techniques had good predictive value against 1 year mortality, with clinically measured NSE from serum being slightly superior to NSE from plasma in predicting mortality.