Background: Vascular access, including arteriovenous fistula (AVF), is essential in patients undergoing hemodialysis (HD). However, the presence of AVF is non-physiological in humans and could pose a burden to the systemic circulation or tissue microcirculation, potentially affecting tissue oxygenation, including in the brain. Recently, near-infrared spectroscopy has been used to measure regional oxygen saturation (rSO2) as a marker of cerebral oxygenation in various settings, including in patients undergoing HD. Thus far, no studies have reported changes in cerebral rSO2 before and after AVF creation. This study aimed to monitor the differences in cerebral oxygenation before and after AVF creation and to clarify the clinical factors affecting the changes in cerebral rSO2. Methods: Forty-eight patients (34 men, 14 women) with chronic kidney disease (CKD) who were not undergoing dialysis and newly created AVF were recruited. Cerebral rSO2 values before and after AVF creation were evaluated using near-infrared spectroscopy (INVOS 5100c). Results: Cerebral rSO2 values were significantly changed from 60.3% ± 7.5% to 58.4% ± 6.8% before and after AVF creation in all patients ( p < 0.001). Cerebral rSO2 were also lower in patients with diabetes mellitus (DM) than in those without DM (57.5 ± 7.1 vs 63.7 ± 6.5, p = 0.003) before surgery; however, no differences of changes in cerebral rSO2 were observed between the two groups after AVF creation. Additionally, multivariate regression analysis identified changes in HR (standardized coefficient: 0.436) as independent factors associated with changes in cerebral rSO2. Conclusion: Surgically created AVF was associated with the deterioration of cerebral rSO2 in patients with CKD not undergoing dialysis. Notably, AVF could cause cerebral hypoxia, and thus further studies are needed to clarify the clinical factors influencing changes in cerebral oxygenation after AVF creation.