Purpose To quantitatively map cerebral metabolic rate of oxygen ( CMRO2) and oxygen extraction fraction ( OEF) in human brains using quantitative susceptibility mapping (QSM) and arterial spin labeling‐measured cerebral blood flow (CBF) before and after caffeine vasoconstriction. Methods Using the multiecho, three‐dimensional gradient echo sequence and an oral bolus of 200 mg caffeine, whole brain CMRO2 and OEF were mapped at 3‐mm isotropic resolution on 13 healthy subjects. The QSM‐based CMRO2 was compared with an R2*‐based CMRO2 to analyze the regional consistency within cortical gray matter (CGM) with the scaling in the R2* method set to provide same total CMRO2 as the QSM method for each subject. Results Compared to precaffeine, susceptibility increased (5.1 ± 1.1 ppb; P < 0.01) and CBF decreased (−23.6 ± 6.7 ml/100 g/min; P < 0.01) at 25‐min postcaffeine in CGM. This corresponded to a CMRO2 of 153.0 ± 26.4 μmol/100 g/min with an OEF of 33.9 ± 9.6% and 54.5 ± 13.2% (P < 0.01) pre‐ and postcaffeine, respectively, at CGM, and a CMRO2 of 58.0 ± 26.6 μmol/100 g/min at white matter. CMRO2 from both QSM‐ and R2*‐based methods showed good regional consistency (P > 0.05), but quantitation of R2*‐based CMRO2 required an additional scaling factor. Conclusion QSM can be used with perfusion measurements pre‐ and postcaffeine vascoconstriction to map CMRO2 and OEF. Magn Reson Med 74:945–952, 2015. © 2014 Wiley Periodicals, Inc.