Background: Acute carbon monoxide (CO) poisoning remains a health concern worldwide and is associated with increased morbidity and mortality. Recognizing critical cases is highly valued to provide early efficient management and improve patient outcomes. Aim: This study aims to measure the partial pressure of carbon dioxide (PaCO2) level in patients with acute CO poisoning and to assess the role of PaCO2 level changes in the outcome of acute CO poisoning . Methods: This prospective study was conducted by collecting demographic, clinical data, blood samples from 35 patients with acute CO poisoning admitted to the Poison Control Center, Ain Shams University. Carboxyhemoglobin (COHb), arterial blood gases and cardiac markers were measured on admission. Results: The studied patients with acute CO poisoning were 20 males (57.1%) and 15 females (42.9%), with an average age of 36.3 ± 13.6 years. Patients had lower than normal levels of PaCO2, pH, and HCO3 and higher than normal levels of troponin I and B-Natriuretic Peptide (BNP). A substantial negative weak to moderate correlation was found between the length of the hospital stay and pH, HCO3 and PaCO2 measurements. On the other hand, BNP had a significant positive moderate correlation with length of hospital stay and a negative correlation with PaCO2. Survivors, displayed significantly higher mean levels of PaCO2, pH and HCO3 than cases who died. Conclusion: The current study suggests that changes in PaCO2 levels play an important role in the outcome of patients with acute CO poisoning, potentially acting as a marker of severity and indicating an increased risk of cardiotoxicity. Lower levels of PaCO2 might be associated with a more severe clinical presentation and poorer prognosis. Clinicians could use PaCO2 as a useful clinical indicator to identify patients at a higher risk of adverse outcomes.