Neurotoxicity is the most serious complication of carbon monoxide (CO) poisoning. The outcome of CO poisoning mostly depends on the severity of CO-induced brain injury. To date, there are scarce studies assessing serum neurogranin (Ng) as a prognostic indicator for CO poisoning severity or predicting poor outcomes. This study aims to evaluate serum Ng's value in these predictions. This prospective cross-sectional study was performed on hundred adult patients diagnosed with acute CO poisoning. Evaluation included GCS, vital signs, PSS, clinical examination, necessary investigations, CT brain, need for ICU, hyperbaric oxygen (HBO), development of delayed neurological sequelae (DNS), and serum Ng levels at three intervals post-exposure. The mean level of serum Ng was significantly higher in patients with more severe poisoning who have lower GCS, higher PSS, hemodynamic instability, metabolic acidosis, and need for ICU or HBO. Serum Ng measures were an early and accurate predictor of the development of brain hypoxic injury and DNS. Serum Ng level at 0 to 6 hours showed perfect discrimination with AUC = 1.0 and both sensitivity and specificity of 100% at a cutoff >424.6 ng/ml in the prediction of brain hypoxic changes before appearing in brain CT. The 24-hour Ng level achieved 100% sensitivity at a cutoff level greater than 442 ng/ml for diagnosing DNS, ensuring that no cases of DNS were missed. In conclusion, Ng is a predictive marker for severe CO poisoning that may require HBO or ICU supportive measures, as well as for the development of DNS.