PURPOSE OF STUDY: Hyperoxia is a significant risk factor for development of retinopathy of prematurity (ROP). Oxygen saturation targets have been widely studied with variable results. We evaluated whether oxygen content was associated with development of ROP. METHODS USED: We retrospectively reviewed charts of infants admitted between January 2013 and December 2016 who were eligible for ROP screening (gestational age ≤30 weeks or birth weight ≤1500 grams) and had arterial blood gases obtained in the first 2 weeks of life. Arterial oxygen content values were collected. Outcomes measured were incidence and severity of ROP. Dell Statistica was used for all statistical analysis. SUMMARY OF RESULTS: There were 305 total infants and 132 had ROP (43.3%). Prevalence of stage 1 was 19.0%, stage 2 was 15.4%, and stage 3 was 8.9%; there were no higher stages of ROP in this population. Decreasing oxygen content within the first 2 weeks of life was significantly associated with higher severity of ROP. Infants without ROP had an average oxygen content of 16.0±6.0 (standard deviation). Average oxygen content for stage 1 was 14.8±4.6, stage 2 was 14.6±4.7, and stage 3 was 13.6±2.4 (p=0.004). CONCLUSIONS: In our population, higher oxygen content levels within the first 2 weeks of life was associated with decreasing severity of ROP development. As previous studies have shown worse ROP with higher saturation targets, this finding is unexpected. Based on our findings, though, oxygen saturations may only be a component of the mechanism leading to the development ROP. There may be further factors not yet studied that may contribute to its development. Further studies are required.(Figure is included in full-text article.)