Background Patients with IDHTN have an increased risk for hospitalizations and mortality. The pathogenesis of IDHTN is not well understood. Hypoxemia is thought to stimulate the blood pressure (BP) elevation. The aim of this work was to study the changes of the arterial oxygen saturation (SaO2) during hemodialysis (HD) and their relations to intradialytic hypertension (IDHTN). Patients and methods This is a prospective observational study that analyzed SaO2 and BP changes during HD sessions in 75 regular HD patients over 6 months. Patients were divided into two groups: group A included patients without intradialytic hypertension (non-IDHTN) and group B included patients with persistent IDHTN group. Results Group B patients had significantly lower predialysis, intradialytic, and postdialysis SaO2 levels compared with group A (P<0.001). Group B patients also showed a significant drop in intradialytic SaO2 compared to group A (P<0.001). There were significant negative correlations between the predialysis, intradialytic, and postdialysis SaO2 and intradialytic systolic blood pressure elevation (P<0.001). It was found that the reduction of the predialysis and intradialytic SaO2 less than 92.5 and 90.5%, respectively, could be predictors of intradialytic systolic blood pressure increase (P<0.001). Conclusion Decreased SaO2 before and during HD sessions may be involved in the induction of IDHTN.