Introduction: Acute carbon monoxide poisoning (ACMP) remains a leading cause of morbidity and mortality from fatal inhaled poisoning. Delayed encephalopathy after ACMP (DEACMP) has become one of the most complex and serious complications. Methods: In this research, an observational study was performed from January 2016 to December 2019 to investigate the potential relevant risk factors of DEACMP with data collected from Level 3 medical facilities located in Northern China. Within the 4-year data collection period, the final study cohort consisted of 240 (117 males, 123 females). Results: Uni-variable analysis identified older age, medical history of cerebrovascular accident, basic disease of diabetes, and longer duration of loss of consciousness as relevant factors for DEACMP; while multivariable logistic regression revealed that the older age (OR, 1.45; 95% CI, 1.25-1.69; P < 0.01), longer duration of loss of consciousness (OR, 1.39; 95% CI, 1.36-1.45; P < 0.01), and cerebrovascular accidents occurring (OR, 1.23; 95% CI, 1.03-1.47; P = 0.04) were independent predictors for DEACMP. Discussion: Furthermore, additional research is needed to testify to the relevance and to elucidate the potential pathogenesis, consequently determining the clinical guideline and approving the best prevention and treatment strategy for DEACMP.