Background.In children with respiratory distress, supplemental oxygen is indicated at oxygen saturation thresholds of 90–94%. However, these thresholds are poorly studied. We conducted a systematic review to summarize the existing evidence for SpO2 thresholds in children with respiratory distress.Methods.Electronic databases and registries were searched for original articles published from January 1st 2010 to February 1st 2022 comparing two or more SpO2 thresholds in children with respiratory distress. Primary outcomes were safety including mortality, neurocognitive outcomes, and readmissions and effectiveness including admission rate and length of hospital stay. Methodological appraisal was performed using the Cochrane RoB-2 or ROBINS-I tools. Results were narratively synthesised.Results.We retrieved 3322 results; 7 studies were included. Lower thresholds ranged from 80% to 92% and were compared with higher thresholds ranging from 92% to 94%. Studies were highly heterogeneous in setting, design, population and outcomes. Risk of bias varied from low to high. Lower SpO2 thresholds had equivalent mortality, neurocognitive outcomes and readmissions or re-attendance to health care as higher thresholds. Lower SpO2 thresholds showed a significant decrease in admission rates by up to 40% and shortened hospitalisation duration by 10 to 18 h.Conclusions.The current SpO2 thresholds of 90–94% in children with respiratory distress may be too high, which could lead to unnecessary hospitalizations and prolonged hospitalisation duration. SpO2 thresholds to levels as low as 88% are potentially safe in children with respiratory distress and may reduce hospitalization rates and length of stay. However, high-quality evidence is needed to support this.