Introduction: Noninvasive hematocrit monitoring (NIVHM) during pediatric hemodialysis (pedHD) provides data in real time regarding changes in hematocrit and blood volume and also provides venous oxygen saturations. The latter has been proposed to indicate changes in tissue oxygen consumption. It is not known how well NIVHM oxygen saturations (O2sat) approximate blood gas measured oximetry saturation (mO2sat) in the course of pedHD. We aimed to assess the validity and reliability of NIVHM O2sat compared to mO2sat. Methods: This is a prospective study in 15 patients <21 years old with >90 days on hemodialysis (HD) without congenital heart disease. HD access was fistula (AVF) in 4 patients and tunneled catheters in the remainder. Pulse oximetry (spO2) was continuously monitored; mO2sat was measured via oximetry in a blood gas analyzer and NIVHM O2sat values collected at the start, middle, and end of HD treatment. Results: A total of 45 dyad measurements were obtained. NIVHM O2sat correlated well with mO2sat ( R = 0.89, p < 0.0001); the same was seen at pre, mid, and post HD time points ( R = 0.86–0.95, p < 0.001). NIVHM O2sat was lower than mO2sat; with catheter as access, the difference was 9.3 ± 8.6 (CI: 12.3–6.22, p < 0.0001) and with AVF was 2.1 ± 0.78 (CI: 2.6–1.7, p < 0.0001). Bland-Altman analysis demonstrated the difference but did not show any systematic bias. Continuous monitor of spO2 showed no hypoxia. Discussion/Conclusion: Intradialytic NIVHM O2sat correlates well with mO2sat but yield lower values. Future studies can include NIVHM O2sat changes as a surrogate for central venous O2 saturation changes and potentially yield useful information regarding tissue oxygen consumption in pedHD patients.