Background: Carbon monoxide (CO) is an odorless, tasteless and colorless gas that causes a potentially fatal illness with a tremendous burden due to significant mortality and morbidity. Carbon monoxide poisoning leads to the development of delayed neurological sequelae (DNS). Aim: To assess the possible risk factors that can predict the development of DNS after acute CO poisoning. Subjects and methods: The patients were recruited between January 2018 and December 2018. The study included 37 cases with acute CO poisoning. The medical history was taken thoroughly. Patients underwent general and neurological clinical assessments with laboratory investigations, including arterial blood gases (ABG), carboxyhemoglobin (COHb), cardiac enzymes, and serum lactate. At the time of admission, all patients were subjected to an electrocardiogram (ECG) and brain imaging (CT or MRI) of the brain. They were followed up three and six months after discharge for complete neurological examination and cognitive functions assessment using the Mini-Mental State Examination (MMSE). Results: Two patients died, both presenting with coma and hemodynamic instability. Five cases were excluded due to a lack of comprehension and refusal to follow-up. Out of the 30 patients who completed the follow-up, 67% survived with no complication, while DNS developed in 33% of the patients. Several predictors for development of DNS were identified. They included lower Glasgow coma score, duration of CO exposure, high COHb level, decrease in blood pH, elevated serum levels of creatine kinase and lactate, and abnormalities in brain structure. The time of DNS development extended to six months post-exposure. Conclusion: We conclude that several clinical and laboratory parameters can predict DNS. Recommendations: proper and accurate clinical and laboratory evaluation of any suspected case of acute CO poisoning should be performed especially those parameters proved to be predictors for DNS. The follow-up of cases should continue at least for six months post-exposure.