Resistance breathing improves tolerance to central hypovolemia induced by lower body negative pressure (LBNP), but this is not related to protection of anterior cerebral blood flow (indexed by mean middle cerebral artery velocity, MCAv). We hypothesized that inspiratory resistance breathing improves tolerance to central hypovolemia by maintaining cerebral oxygenation (ScO₂), and protecting cerebral blood flow in the posterior cerebral circulation (indexed by posterior cerebral artery velocity, PCAv). Eight subjects (4M/4F) completed two experimental sessions of a presyncopal-limited LBNP protocol (3 mmHg/min onset rate) with and without (Control) resistance breathing via an impedance threshold device (ITD). ScO₂ (via near-infrared spectroscopy), MCAv and PCAv (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Hemodynamic responses were analyzed between the Control and ITD condition at baseline (T1) and the time representing 10-s prior to presyncope in the Control condition (T2). While breathing on the ITD increased LBNP tolerance from 1506±75 s to 1704±88 s (P=0.003), both mean MCAv and mean PCAv were similar between conditions at T2 (P≥0.46), and decreased by the same magnitude with and without ITD breathing (P≥0.53). ScO₂ also decreased by approximately 9% with or without ITD breathing at T2 (P=0.972), and there were also no differences in deoxygenated (dHb) or oxygenated hemoglobin (HbO2) between conditions at T2 (P≥0.43). There was no evidence that protection of regional cerebral blood velocity (i.e., anterior or posterior cerebral circulation), nor cerebral oxygen extraction played a key role in the determination of tolerance to central hypovolemia with resistance breathing.