We have shown that performing blood flow restriction (BFR) during low-intensity aerobic exercise can trigger local and systemic hypoalgesia, which is not typically observed with this intensity of exercise. High-pressure BFR triggers greater and comparable hypoalgesia than high-intensity aerobic exercise in the exercising limbs and remote areas of the body, respectively. Performing BFR during low-intensity aerobic exercise activates the opioid and endocannabinoid systems, providing novel insight into potential mechanisms of hypoalgesia with BFR exercise