Estimation of the cerebral metabolic rate of oxygen (CMRO 2) and cerebral blood flow (CBF) is important to investigate the neurovascular coupling and physiological components in blood oxygenation level-dependent (BOLD) signals quantitatively. Although there are methods that can determine CMRO 2 changes using functional MRI (fMRI) or near-infrared spectroscopy (NIRS), current approaches require a separate hypercapnia calibration process and have the potential to incur bias in many assumed model parameters. In this paper, a novel method to estimate CMRO 2 without hypercapnia is described using simultaneous measurements of NIRS and fMRI. Specifically, an optimization framework is proposed that minimizes the differences between the two forms of the relative CMRO 2-CBF coupling ratio from BOLD and NIRS biophysical models, from which hypercapnia calibration and model parameters are readily estimated. Based on the new methods, we found that group average CBF, CMRO 2, cerebral blood volume (CBV), and BOLD changes within activation of the primary motor cortex during a finger tapping task increased by 39.5 ± 21.4%, 18.4 ± 8.7%, 12.9 ± 6.7%, and 0.5 ± 0.2%, respectively. The group average estimated flow-metabolism coupling ratio was 2.38 ± 0.65 and the hypercapnia parameter was 7.7 ± 1.7%. These values are within the range of values reported from other literatures. Furthermore, the activation maps from CBF and CMRO 2 were well localized on the primary motor cortex, which is the main target region of the finger tapping task. © 2010 Institute of Physics and Engineering in Medicine.