Recent studies postulated that increased oxygenation of the prefrontal cortex (PFC) during elevating exercise intensities reflects a specific activation of this region. Furthermore, the drop in PFC oxygenation often measured shortly before exhaustion is interpreted as a main factor limiting exercise. Nevertheless, a limitation of these studies is that they often measured NIRS only in the PFC. Within this study, we hypothesized that these findings are not region specific but rather result from systemic blood redistribution to the working skeletal muscle. NIRS was measured in three different brain regions and the working skeletal muscle during incremental cycling till exhaustion in nine healthy men. Oxygenated hemoglobin of the PFC increased from low to submaximal intensities and leveled off at maximal intensities. There was no drop in PFC oxygenation before exercise abortion. Interestingly, the occipital cortex was unaffected during exercise, while the motor cortex showed an increasing deoxygenation with elevating exercise intensities, just as observed in the skeletal muscle. In conclusion, this study does not support the notion that PFC deoxygenation is involved in the limitation of maximum exercise capacity. Against the hypothesis, the NIRS signals of the other cortices differed clearly, indicating that the previously reported findings indeed represent region-specific activations.