Purpose: The objective of this study was to demonstrate the feasibility of a cerebral metabolic rate of oxygen (CMRO 2 ) mapping method based on its minimum local variance (MLV) without vascular challenge using quantitative susceptibility mapping (QSM) and cerebral blood flow (CBF). Methods: Three-dimensional multi-echo gradient echo imaging and arterial spin labeling were performed in 11 healthy subjects to calculate QSM and CBF. Minimum local variance was used to compute whole-brain CMRO 2 map from QSM and CBF. The MLV method was compared with a reference method using the caffeine challenge. Their agreement within the cortical gray matter (CGM) was assessed on CMRO 2 and oxygen extraction fraction (OEF) maps at both baseline and challenge states. Results: Mean CMRO 2 (in mmol/100 g/min) obtained in CGM using the caffeine challenge and MLV were 142 6 16.5 and 139 6 14.8 mmol/100 g/min, respectively; the corresponding baseline OEF were 33.0 6 4.0% and 31.8 6 3.2%, respectively. The MLV and caffeine challenge methods showed no statistically significant differences across subjects with small ( < 4%) biases in CMRO 2 and OEF values. Conclusions: Minimum local variance-based CMRO 2 mapping without vascular challenge using QSM and arterial spin labeling is feasible in healthy subjects. Magn Reson Med 79:172-179,