Inadequate cerebral perfusion is a risk factor for cerebral ischemia in patients with large artery steno-occlusion. We investigated whether prefrontal oxyhemoglobin oscillation (Delta HbO(2), 0.6-2 Hz) was associated with decreased vascular reserve in patients with steno-occlusion in the large anterior circulation arteries. Thirty-six patients with steno-occlusion in the anterior circulation arteries (anterior cerebral artery, middle cerebral artery, and internal carotid artery) were included and compared to thirty-six control subjects. Patients were categorized into two groups (deteriorated vascular reserve vs. preserved vascular reserve) based on the results of Diamox single- photon emission computed tomography imaging. HbO(2) data were collected using functional near-infrared spectroscopy. The slope of Delta HbO(2) and the ipsilateral/contralateral slope ratio of Delta HbO(2) were analyzed. Among the included patients (n=36), 25 (69.4%) had deteriorated vascular reserve. Patients with deteriorated vascular reserve had a significantly higher average slope of Delta HbO(2) on the ipsilateral side (5.01 +/- 2.14) and a higher ipsilateral/contralateral ratio (1.44 +/- 0.62) compared to those with preserved vascular reserve (3.17 +/- 1.36, P=0.014; 0.93 +/- 0.33, P=0.016, respectively) or the controls (3.82 +/- 1.69, P=0.019; 0.94 +/- 0.29, P=0.001). The ipsilateral/contralateral Delta HbO(2) ratio could be used as a surrogate for vascular reserve in patients with severe steno-occlusion in the anterior circulation arteries.