Near-infrared spectroscopy (NIRS) is used to monitor cerebral tissue oxygenation (rSO₂) depending on cerebral blood flow (CBF), cerebral blood volume and blood oxygen content. We explored whether NIRS might be a more easy applicable proxy to [¹⁵O]H₂O positron emission tomography (PET) for detecting CBF changes during hemodialysis. Furthermore, we compared potential determinants of rSO₂ and CBF. In 12 patients aged ≥ 65 years, NIRS and PET were performed simultaneously: before (T1), early after start (T2), and at the end of hemodialysis (T3). Between T1 and T3, the relative change in frontal rSO₂ (ΔrSO₂) was −8 ± 9% ( P = 0.001) and −5 ± 11% ( P = 0.08), whereas the relative change in frontal gray matter CBF (ΔCBF) was −11 ± 18% ( P = 0.009) and −12 ± 16% ( P = 0.007) for the left and right hemisphere, respectively. ΔrSO₂ and ΔCBF were weakly correlated for the left (ρ 0.31, P = 0.4), and moderately correlated for the right (ρ 0.69, P = 0.03) hemisphere. The Bland-Altman plot suggested underestimation of ΔCBF by NIRS. Divergent associations of pH, pCO₂ and arterial oxygen content with rSO₂ were found compared to corresponding associations with CBF. In conclusion, NIRS could be a proxy to PET to detect intradialytic CBF changes, although NIRS and PET capture different physiological parameters of the brain.