Introduction Cognitive impairment and exercise intolerance are common in dialysis patients. Cerebral perfusion and oxygenation play a major role in both cognitive function and exercise execution; HD session per se aggravates cerebral ischemia in this population. This study aimed to compare cerebral oxygenation and perfusion at rest and in mild physical stress between HD and PD patients, as well as controls without CKD. Methods Eighty-one participants (27 HD, 27 PD and 27 controls, matched for age, sex) underwent a 3-min intermittent-handgrip-exercise at 35% of their maximal-voluntary-contraction (MVC). During exercise, cerebral oxygenation (oxyhemoglobin-O2Hb, deoxyhemoglobin-HHb, total-hemoglobin-tHb) was assessed by near-infrared-spectroscopy. Results Age, sex, dialysis-vintage, and major comorbidities did not differ between groups. The average increases observed during exercise in O2Hb (cerebral oxygenation index) were significantly impaired in both dialysis modalities compared to controls, with HD patients tending to have lower levels (HD: 1.20 ± 1.03 vs. PD: 1.53 ± 0.99 vs. Controls: 2.41 ± 1.35 μmol/L, p = 0.001). Similarly, the average HHb and tHb (HD: 0.57 ± 1.20 vs. PD: 1.21 ± 1.11 vs. Controls: 2.21 ± 1.50 μmol/L, p textless 0.001) responses were significantly lower in both dialysis groups compared to controls, with a trend toward lower levels in HD patients. As for Hbdiff, a significant trend for lower values in both dialysis modalities compared to controls was observed, with no marked numerical differences between them. Blunted average responses in O2Hb, tHb, and Hbdiff were associated with more impaired cognitive performance (MMSE score). Conclusions Cerebral oxygenation is blunted in both HD and PD, while HD individuals exhibit a trend toward even lower levels, potentially reflecting the cumulative cerebrovascular stress associated with intermittent dialysis.