Background This study investigated the long-term effects of multiple concussions on prefrontal cortex oxygenation using near-infrared spectroscopy (NIRS) during a squat-stand maneuver that activated dynamic cerebral autoregulation. Methods Active male retired contact sport athletes with a history of 3+ concussions (mTBI; n = 55), and active retired athletes with no concussion history (CTRL; n = 29) were recruited. Participants completed a 5-min squat-stand maneuve (10-s squat, 10-s stand, 0.05 Hz; 15 times). Oxygenated (O2Hb), deoxygenated (HHb), total (tHb) hemoglobin, and hemoglobin difference (HbDiff) were analyzed through the change in maximal and minimal values during the test (∆MAX), Z-scores, and standard deviations. Results mTBI group showed left prefrontal cortex O2Hb ∆MAX (p = 0.046) and HbDiff ∆MAX (p = 0.018) were significantly higher. Within-group analyses showed significantly higher left HHb ∆MAX (p = 0.003) and lower left HbDiff Z-scores (p = 0.010) only in the mTBI group. The CTRL group demonstrated significantly lower left HbDiff SD (p = 0.039), tHb Z-scores (p = 0.030), and HbDiff ∆MAX (p = 0.037) compared to right prefrontal cortex response. Conclusion These preliminary results suggest changes in prefrontal cortex oxygenation potentially affecting the brain’s ability to adapt to changing cerebral perfusion pressure after multiple previous concussions.