Purpose: This study examined the association between smoking and delayed neuropsychological sequelae (DNS) in acute carbon monoxide (CO) poisoning. Methods: Patients admitted to the medical center emergency department from March 2016 to March 2017 because of CO poisoning were examined retrospectively. The patients were divided into two groups: DNS and Non-DNS group. Multiple factors were analyzed to explain DNS, which was assessed by motor disturbances, cognitive impairment, dysphagia, Parkinson-like syndromes, epilepsy, and emotional lability in CO poisoning. Results: A total of 120 patients were included. The factors related to DNS were smoking (pack-years) (p=0.002) and initial carbon monoxide-hemoglobin level (p=0.015). On the other hand, after multivariate logistic regression analysis, smoking (Odds ratio 1.07; 95% CI, 1.02-1.13; p=0.004) was the only factor associated with DNS. Conclusion: Smoking is a very reliable factor for predicting the occurrence of DNS. A history of smoking in patients who suffer from CO intoxication is important. If a patient smokes, treatment should be started actively and as soon as possible.