This exploratory study aimed to investigate the long-term effects of multiple concussions on prefrontal cortex oxygenation during a five-minute hypercapnic challenge using Near Infrared Spectroscopy (NIRS). 55 physically active retired contact sport male athletes with three or more previous concussions (mTBI) were recruited along with 29 physically active males with no concussions history (CTRL). Participants completed five minutes of seated rest prior to the five-minute hypercapnic challenge (20-second breath-hold, 40-second recovery breathing; five times). NIRS measured right and left side oxygenated (O2Hb), deoxygenated (HHb), total (tHb) haemoglobin, and haemoglobin difference (HbDiff) with all parameters analysed through changes in average maximal and minimal values (ΔMAX), Z-scores, and standard deviations. Right prefrontal cortex HbDiff ΔMAX was significantly higher in the mTBI compared to CTRL (p = 0.045) group. Left prefrontal cortex O2Hb ΔMAX (p = 0.040), HHb Z-Scores (p = 0.008), and HbDiff ΔMAX(p = 0.014) were significantly higher in the mTBI group. Within-group right vs left analyses demonstrated significantly lower left HbDiff ΔMAX (p = 0.048) and HbDiff Z-scores (p = 0.002) in the mTBI group, while the CTRL group had significantly lower left HHb Z-scores (p = 0.003) and left tHb Z-scores (p = 0.042). This study provides preliminary evidence that athletes with a history of three or more concussions may have impaired prefrontal cortex oxygenation parameters during a hypercapnic challenge.