Objective To explore effects of hyperbaric oxygen therapy in the treatment of acute moderate to severe carbon monoxide poisoning and in prevention of delayed encephalopathy. Methods 120 patients with CO poisoning treated in the Affiliated Hospital of North Sichuan Medical College from January 2016 to December 2019 were enrolled in the prospective study. They were divided into control group and observation group by number table method with 60 patients in each group. The control group was given routine treatment and the observation group was given hyperbaric oxygen therapy. The therapeutic effects, changes in oxidative stress indexes before and after treatment, level of consciousness ［Glasgow coma score (GCS)］, extent of neurological damage ［neurological deficit score (NFDS)］, activities of daily living ［Barthel Index (BI)］ scores and incidence of delayed encephalopathy were compared between the two groups. ResultsThe total response rate in the observation group (91.67%) was significantly higher than that in the control group (7667%) (P＞0.05). There was no significant difference in the latency or amplitude of the eventrelated potential P300 at the electromyogram evoked potential FZ site and PZ site between the two groups before treatment (P＞0.05). After treatment, the above indexes were improved, and the improvement was better in the observation group than the control group (P＜0.05). Before treatment, there were no significant differences in oxidative stress indexes between the two groups (P＞0.05). After treatment, superoxide dismutase (SOD) levels increased, while malondialdehyde (MDA) and neuronspecific enolase (NSE) levels decreased. SOD levels in the observation group were significantly higher than those in the control group, while MDA and NO levels were significantly lower than the control group (P＜0.05). Before treatment, there were no significant differences in GCS scores, NFDS score or BI scores between the two groups (P＞0.05). After treatment, GCS scores and BI scores of the observation group were significantly higher than the control group, while NFDS scores were significantly lower than the control group (P＞0.05). During treatment, there was 1 case with insomnia and 1 case with nausea and vomiting in the control group, with an incidence of adverse reactions of 333%. There was only 1 case with anorexia in the observation group, and the incidence of adverse reactions was 1.67% (P＞0.05). 3 monthslater, follow-up results showed 2 cases of delayed encephalopathy in the observation group, accounting for 333%, and 8 cases in the control group, accounting for 1333% (2=3.927,P=0.048). Conclusion Compared with routine treatment, the effect of hyperbaric oxygen therapy is better in the treatment of acute moderate to severe carbon monoxide poisoning. The latter can promote brain blood circulation, effectively alleviate patients’ oxidative stress status, reduce the degree of neurological damage, and promote the recovery of cognitive function and activities of daily living, with few side effects. It also can reduce the incidence of delayed encephalopathy.