Importance: Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice. Objective: To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes. Data Sources: Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance. Study Selection: Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2results were excluded. Data Extraction and Synthesis: Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models. Main Outcomes and Measures: The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao2, UA base excess, 1-and 5-minute Apgar scores, and neonatal intensive care unit admission. Results: The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I2= 49.88%; P =.03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI,-0.01 to 0.01). Oxygen use was associated with an increase in UA Pao2(weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao2(weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI,-0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11). Conclusions and Relevance: This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.