This study tested the hypothesis that muscle blood flow restriction reduces muscle and cerebral oxygenation, at rest. In 26 healthy males, aged 33±2 yrs, physiological variables were continuously recorded during a 10-min period in two experimental conditions: a) with muscle blood flow restriction through thigh cuffs application inflated at 120 mmHg (With Cuffs, WC) and b) without restriction (No Cuffs, NC). Muscle and cerebral oxygenation were reduced by muscle blood flow restriction as suggested by the increase in both muscle and cerebral deoxygenated hemoglobin ($Δ$[HHb]; p<0.01) and the decrease of muscle and cerebral oxygenation index ($Δ$[HbDiff]; p<0.01). Hemodynamic responses were not affected by such muscle blood flow restriction, whereas baroreflex sensitivity was reduced (p=0.009). The perception of leg discomfort was higher (p<0.001) in the WC than in the NC condition. This study suggests that thigh cuffs application inflated at 120 mmHg is an effective method to reduce muscle oxygenation at rest. These changes at the muscular level seem to be sensed by the central nervous system, evoking alterations in cerebral oxygenation and baroreflex sensitivity. Novelty bullets: • Thigh cuffs application inflated at 120 mmHg effectively reduces muscle oxygenation at rest. • Limiting muscle oxygenation appears to reduce cerebral oxygenation, and baroreflex sensitivity, at rest. • Even in healthy subjects, limiting muscle oxygenation, at rest, affects neural integration.