The global cerebral metabolic rate of oxygen (CMRO2), which reflects metabolic activity of the brain under various physiologic conditions, can be quantified using a method, referred to as ‘OxFlow’, which simultaneously measures hemoglobin oxygen saturation in a draining vein (Yv) and total cerebral blood flow (tCBF). Conventional OxFlow (Conv-OxFlow) entails four interleaves incorporated in a single pulse sequence – two for phase-contrast based measurement of tCBF in the supplying arteries of the neck, and two to measure the intra- to extravascular phase difference in the superior sagittal sinus to derive Yv [Jain et al., JCBFM 2010]. However, this approach limits achievable temporal resolution thus precluding capture of rapid changes of brain metabolic states such as the response to apneic stimuli. Here, we developed a time-efficient, multiplexed OxFlow method and evaluated its potential for measuring dynamic alterations in global CMRO2 during a breath-hold challenge. Two different implementations of multiplexed OxFlow were investigated: 1) simultaneous-echo-refocusing based OxFlow (SER-OxFlow) and 2) simultaneous-multi-slice imaging-based dual-band OxFlow (DB-OxFlow). The two sequences were implemented on 3 T scanners (Siemens TIM Trio and Prisma) and their performance was evaluated in comparison to Conv-OxFlow in ten healthy subjects for baseline CMRO2 quantification. Comparison of measured parameters (Yv, tCBF, CMRO2) revealed no significant bias of SER-OxFlow and DB-OxFlow, with respect to the reference Conv-OxFlow while improving temporal resolution two-fold (12.5 versus 25 s). Further acceleration shortened scan time to 8 and 6 s for SER and DB-OxFlow, respectively, for time-resolved CMRO2 measurement. The two sequences were able of capturing smooth transitions of Yv, tCBF, and CMRO2 over the time course consisting of 30 s of normal breathing, 30 s of volitional apnea, and 90 s of recovery. While both SER- and DB-OxFlow techniques provide significantly improved temporal resolution (by a factor of 3 – 4 relative to Conv-OxFlow), DB-OxFlow was found to be superior for the study of short physiologic stimuli.