Risk factors for hypoxemia in school age children undergoing one-lung ventilation remain poorly understood. We hypothesize that certain modifiable and non-modifiable factors may be associated with increased risk of hypoxemia in school age children undergoing one-lung ventilation and thoracic surgery. The Multicenter Perioperative Outcomes Group database was queried for children 4 to 17 years of age undergoing one-lung ventilation. Patients undergoing vascular or cardiac procedures were excluded. The original cohort was divided into two cohorts: 4-9 and 10-17 years of age inclusive. All records were reviewed electronically for the primary outcome of hypoxemia during one-lung ventilation defined as an oxygen saturation (SpO2)<90% for≥3 minutes continuously and severe hypoxemia, SpO2<90% for ≥5 minutes. Potential modifiable and non-modifiable risk factors associated with these outcomes were evaluated using separate multivariable least absolute shrinkage and selection operator regression analyses for each cohort. Covariates evaluated included: age, extremes of weight, American Society of Anesthesiologists Physical Status≥3, duration of one-lung ventilation, preoperative SpO2<98%, approach to one lung ventilation, right operative side, video assisted thoracoscopic surgery, lower tidal volume ventilation defined as tidal volume≤6ml/kg + positive end expiratory pressure ≥ 4cmH2O >80% of the duration of one-lung ventilation, and procedure type. The prevalence of hypoxemia in the 4-9 and 10-17 year old cohorts was 24/228 (10.5%, 95%CI[6.5%-14.5%]) and 76/1012 (7.5%, 95%CI[5.9%-9.1%]) respectively. The prevalence of severe hypoxemia in both cohorts was 14/228 (6.1%, 95%CI[3.0%-9.3%]) and 47/1012 (4.6%, 95%CI[3.3%-5.8%]). Initial SpO2<98% was associated with hypoxemia in the 4-9 year old cohort, OR 4.20 [95%CI(1.61 - 6.29)]. Initial SpO2<98%, OR 2.76[95%CI(1.69-4.48)], extremes of weight, OR 2.18[95%CI(1.29-3.61)], right sided cases, OR 2.33[95%CI(1.41-3.92)], were associated with an increased risk of hypoxemia in the older cohort. Increasing age (1 year increment), OR 0.88[95%CI(0.80-0.97)] was associated with a decreased risk of hypoxemia. An initial room air oxygen saturation <98% was associated with an increased risk of hypoxemia in all children 4-17 years of age. Extremes of weight, right sided cases, and decreasing age were associated with an increased risk of hypoxemia in children 10-17 years of age.