Objective To explore the clinical significance of BIS, NLR and Copeptin for prognostic outcome in patients with acute severe carbon monoxide poisoning (ASCOP). Methods 157 ASCOP patients occurred from October 2018 to February 2021 were divided into cure group(82)，delayed encephalopathy group (DEACMP) (51) and death group(24). Changes in high-sensitive troponin I (hs-TnI)，creatine kinase isoenzyme (CK-MB)，soluble growth stimulus expression gene 2 protein (sST2)，and peptidoginin (Copeptin)，N L R，and B I S values were examined at 24 h， 3 d， 5 d，after discharge from the hospital admission. Results Comparison between sex， age in the cure， DEACMP，and death groups showed no statistical difference between groups (P>0.05). Comparisons between CO monoxide exposure，coma，and acute physiology and chronic health score system (APACHEⅡ)  scores were statistically significant (P<0.05). The hs-TnI，CK-MB，Copeptin，sST2， NLR， BIS values 24 h， 3 d， 5 d in the cure， DEACMP and death groups were statistically significant (P＜0.05). The cure DEACMP，and death groups，compared the change trends in hs-TnI，CK-MB，Copeptin， sST2， NLR， BIS values，with statistically significant differences (P<0.05). The APACHE score was negatively correlated with BIS values (r= 0.781， P<0.004) and a positive correlation with NLR (r=0.737， P<0.006). The results using the receiver operating characteristic curve (ROC) showed that the area under the 24h， BIS， NLR joint detection curve after admission was 0.829，with the greatest predictive value for outcome in ASCOP patients. Conclusion Dynamic detection of BIS and NLR has important clinical value for early prediction of prognostic outcome in ASCOP patients.