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Generating 10-s (∼0.1 Hz) fluctuations or "oscillations" in arterial pressure and blood flow blunts reductions in cerebral tissue oxygenation in response to 15%–20% reductions in cerebral blood flow. To examine the effect of 0.1 Hz hemodynamic oscillations on tissue oxygenation during severe ischemia, we developed a partial limb ischemia protocol targeting a 70%–80% reduction in blood flow. We hypothesized that 0.1 Hz hemodynamic oscillations would attenuate reductions in tissue oxygenation during severe ischemia. Thirteen healthy humans (6 M and 7 F; 27.3 ± 4.2 yr) completed two experimental protocols separated by ≥48 h. In both conditions, an upper arm cuff was used to decrease brachial artery (BA) blood velocity by ∼70%–80% from baseline. In the oscillation condition (0.1 Hz), 0.1 Hz hemodynamic oscillations were induced by intermittently inflating and deflating bilateral thigh cuffs every 5 s during forearm ischemia. In the control condition (0 Hz), the thigh cuffs were inactive. BA blood flow, forearm tissue oxygenation (SmO2), and arterial pressure were measured continuously. The initial reduction in BA blood velocity was tightly matched between protocols (0 Hz: −76.9 ± 7.9% vs. 0.1 Hz: −75.5 ± 7.4%, P = 0.49). Although 0.1 Hz oscillations during forearm ischemia had no effect on the reduction in BA velocity (0 Hz: −73.0 ± 9.9% vs. 0.1 Hz: −73.3 ± 8.2%, P = 0.91), the reduction in SmO2 was attenuated (0 Hz: −35.7 ± 8.6% vs. 0.1 Hz: −27.2 ± 8.9%, P = 0.01). These data provide further evidence for the use of 0.1 Hz hemodynamic oscillations as a potential therapeutic intervention for conditions associated with severe tissue ischemia (e.g., hemorrhage and stroke). NEW & NOTEWORTHY: We investigated the effects of induced 10-s (0.1 Hz) oscillations in blood flow on forearm tissue oxygenation during severe ischemia. Intermittent inflation of bilateral thigh cuffs was used as a clinically applicable method to drive blood flow oscillations. In support of our hypothesis, 0.1 Hz oscillations in blood flow blunted reductions in forearm tissue oxygenation. These results further support the potential use of oscillatory hemodynamics as a therapeutic intervention for ischemic conditions. [ABSTRACT FROM AUTHOR]