Purpose <p>Sufficient blood and oxygen supply to the brain is crucial for optimal performance. This study examined the effects of endurance training on oxygen delivery to the right and left prefrontal cortex.</p> Methods <p>Sixteen male distance runners (age: 34.1 ± 5.1 yrs, weight: 70.8 ± 4.1&#xa0;kg) trained five times per week for eight weeks. Training included two high-intensity interval sessions (90–100% VO₂max) and three continuous sessions (70–80% VO₂max). Before and after training VO₂max was assessed in running and cycling. Deoxyhemoglobin (HHb), oxyhemoglobin (O₂Hb) total hemoglobin (tHb), and tissue saturation index (TSI) were recorded using functional multichannel near-infrared spectroscopy to assess oxygenation in the left and right prefrontal cortex, the vastus lateralis, and the biceps brachialis (inactive muscle) during 10-min of submaximal cycling performed at an intensity 5% below the first ventilatory threshold.</p> Results <p>VO₂max increased in both running (+ 6.1%) and cycling (+ 5.8%) (<i>p</i> &lt; 0.01). During the 10-min submaximal exercise post training increases were observed in O₂Hb (+ 27.7%), HHb (+ 37.9%) and THb (+ 30.6%) in the right prefrontal cortex (<i>p</i> &lt; 0.01) and in O₂Hb (+ 23.2%), HHb (+ 41%) and THb (+ 29.4%) in the left prefrontal cortex (<i>p</i> &lt; 0.01). However, TSI decreased in the left (-9.8%, <i>p</i> &lt; 0.05), but remained unchanged in the right prefrontal cortex. In the vastus lateralis, O₂Hb (-27.1%), THb (-18.7%) and TSI (-10.4%) decreased (<i>p</i> &lt; 0.05). In the inactive biceps brachii muscle O₂Hb and THb increased (+ 59% and + 44%) (<i>p</i> &lt; 0.05).</p> Conclusions <p>Endurance training facilitate redistribution of blood volume from the muscle to the brain enhancing oxygen delivery. The right and left prefrontal cortex appear to adapt differently to endurance training, suggesting distinct functions in regulating aerobic exercise tolerance.</p>