Introduction: Remote ischemic preconditioning (RIPC) is characterized by the cyclic application of limb blood flow restriction and reperfusion, and has been shown to protect the brain during a subsequent ischemic insult. Blood flow restriction exercise (BFRE) is a novel training modality that similarly combines bouts of blood flow restriction and reperfusion with low-intensity exercise and thus could potentially emulate the protection demonstrated by RIPC. One concern with clinical application of BFRE is the potential for an augmented exercise pressor reflex, resulting in an unsafe rise in sympathetic outflow. Due to the use of lower workloads, however, we hypothesized that BFRE would exhibit an attenuated increase in sympathetic outflow, mean arterial pressure (MAP), and brain blood flow. Methods: 11 subjects (6M/5F; age 28±2 yrs) underwent 2 leg press exercise interventions separated by ≥1 month: 1. BFRE - 220 mmHg thigh occlusion during 4 cycles x 5-min of exercise, consisting of 3 x 10 reps at 20% of 1 rep-max (1RM), and; 2. Conventional exercise (CE) - 4 cycles x 5-min of exercise, consisting of 3 x 10 reps at 65% 1RM without occlusion. 5-min of rest and reperfusion (for BFRE) followed each cycle. MAP, mean middle cerebral artery velocity (MCAv), cerebral oxygen saturation (ScO 2 ), and plasma norepinephrine concentrations ([NE]) were compared between trials. Results: MAP increased with exercise under both conditions (P<0.001) and was higher (P≤0.03) with CE vs. BFRE for each cycle (1. 107±3 vs. 103±2 mmHg, 2. 107±2 vs. 103±2 mmHg, 3. 107±2 vs. 103±2 mmHg, 4. 107±2 vs. 104±2 mmHg). MCAv and ScO 2 (N=10) increased over time (P<0.001) with no difference between conditions for MCAv (P=0.83), while ScO 2 was higher for CE vs. BFRE (65±1 vs. 62±1%, P=0.05). Plasma [NE] (N=7) increased over time for both conditions (P=0.08) and was higher for CE vs. BFRE (757±103 vs. 524±71 pg/ml, P=0.09). Conclusions: BFRE elicited an attenuated sympathetic response compared to CE as evidenced by lower MAP and plasma [NE]. The lower ScO 2 (i.e., increased oxygen extraction) and no difference in MCAv responses suggests greater cerebral metabolic demand with BFRE. These findings indicate that BFRE could be explored as an alternative to CE in the clinical setting such as stroke-rehabilitation.