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The occlusion of the common carotid artery (CCA) during carotid endarterectomy (CEA) is associated with a risk of cerebral ischemia due to inadequate collateral blood flow¹. By monitoring tissue oxygen saturation (StO₂), near‐infrared spectroscopy (NIRS) is frequently employed during CEA² to determine sufficient oxygen delivery. However, StO₂ is only a proxy of oxygen metabolism and an unreliable marker of ischemic injury. In contrast, cytochrome c oxidase (oxCCO) is an enzyme in the mitochondrial electron transport chain and therefore a specific marker of aerobic metabolism³. Thus, the aim of this study was to assess the ability of a multi‐distance hyperspectral (hs) NIRS to monitor changes in StO₂ and oxCCO during CCA compressions in healthy participants. We hypothesized that changes in oxCCO concentration would be greater in the brain (i.e., long source‐detector distance, SDD) than …