Carbon monoxide (CO) is the second most frequent environmental pollutant worldwide. Tissue hypoxia appears to be the main cause that stands behind the harmful effects of co-poisoning. This study aimed to improve the management of carbon monoxide-intoxicated patients by predicting of use of erythropoietin levels in determining the need for hyperbaric oxygen (HBO) treatment in CO-poisoned patients who were previously categorized as non-HBO needers according to COHB level that was found to be below 25%. This cross-sectional comparative study was carried out on 71 patients presented to the Poison Control Center of Minia University with a history of CO poisoning from 1st February 2020 to April 2022. Arterial blood samples were drawn for carboxyhemoglobin (COHb) level, venous blood samples were drawn on admission, and after 2 hours from patients who had COHb < 25 % for erythropoietin (EPO) value, CT and ECG were performed to all patients. We demonstrated that 23 patients had COHb > 25 %, and 48 patients had COHb < 25 %, EPO predicted the need for HBO in 17 patients after 2 hours with a sensitivity of 82.35 % and specificity of 100 %. So we concluded that EPO was a good predictor for the need for HBO in CO-poisoned patients with COHb less than 25%.