The cerebral metabolic rate of oxygen (CMRO2) is considered a robust marker of the infarct core in 15°-tracer- based positron emission tomography. We aimed to delineate the infarct core in patients with acute ischemic stroke using commonly used relative cerebral blood flow (rCBF) < 30% and oxygen metabolism parameter of CMRO2 on CT perfusion in comparison with pre-treatment diffusion- weighted imaging (DWI)-derived infarct core volume. Patients with acute ischemic stroke who met the inclusion criteria were recruited. The CMRO2 and CBF maps in CT perfusion were automatically generated using post-processing software. The infarct core volume was quantified with relative (r) CMRO2 < 20% - 30% and rCBF < 30%. The optimal threshold was defined as those that demonstrated the smallest mean absolute error, lowest mean infarct core volume difference, narrowest 95% limit of agreement, and largest intraclass correlation coefficient (ICC) against the DWI. This study included 76 patients (mean age ± standard deviation, 69.97 ± 12.15 years, 43 males). The optimal thresholds of rCMRO2 < 26% resulted in the lowest mean infarct core volume difference, narrowest 95% limit of agreement, and largest ICC among different thresholds. Bland-Altman analysis demonstrated a volumetric bias of 1.96 mL between DWI and rCMRO2 < 26%, whereas in cases of DWI and rCBF < 30%, the bias was notably larger at 14.10 mL. The highest correlation was observed for rCMRO2 < 26% (ICC=0.936), whereas rCBF < 30% showed a slightly lower ICC of 0.934. CT perfusion-derived CMRO2 is a promising parameter for estimating the infarct core volume in patients with acute ischemic stroke. CMRO2 = cerebral metabolic rate of oxygen.