Abstract. OBJECTIVES: To assess the effect of early exposure to O2 and parenteral nutrition (PN) on oxidative stress at 36 weeks post-menstrual age (PMA) and on bronchopulmonary dysplasia (BPD) in extremely preterm infants. STUDY DESIGN: A prospective observational study including 116 infants <29 weeks of gestation. Baseline clinical characteristics, FiO2 on day 7, duration of PN and clinical outcomes data were collected. In 39 infants, whole blood glutathione (GSH) and oxidized glutathione (GSSG) at 36 weeks PMA were measured and the redox potential was calculated using Nernst equation. Student’s t-test, Chi-square, Spearman correlation, ANOVA, and logistic regression analyses were used as appropriate. P < 0.05 was considered significant. RESULTS: FiO2 ≥25% was associated with higher level of GSSG (0.29 ± 0.04 versus 0.18 ± 0.02 nmol/mg of protein), a more oxidized redox potential (–191 ± 2 versus –198 ± 2 mV) and more BPD (90% versus 45%). PN duration >14 days was also associated with higher level of GSSG (0.26 ± 0.03 versus 0.13 ± 0.02 nmol/mg of protein), a more oxidized redox potential (–193 ± 5 versus –203 ± 2 mV) and more BPD (89% versus 24%). In logistic regression model, each 1% increase in FiO2 and each day increase in PN duration resulted in an increase in the OR for BPD by1.57 (1.09 –2.28) and 1.17 (1.03 –1.33) respectively. CONCLUSION: Early O2 supplement and PN have additive effects that were associated with prolonged oxidative stress and increased risk of BPD. Strategies targeting judicious use of O2 and decreasing the duration or developing a safer formulation of PN can be targeted to decrease BPD.