Objectives:: The objective of this study was to define the association between the burden of severe hypoxemia (SpO 2 ≤70%) in the first week of life and development of severe ICH (grade III/IV) in preterm infants. Study design:: Infants born at <32 weeks or weighing <1500 g underwent prospective SpO 2 recording from birth through 7 days. Severe hypoxemia burden was calculated as the percentage of the error-corrected recording where SpO 2 ≤70%. Binary logistic regression was used to model the relationship between hypoxemia burden and severe ICH. Results:: A total of 163.3 million valid SpO 2 data points were collected from 645 infants with mean EGA = 27.7 ± 2.6 weeks, BW = 1005 ± 291 g; 38/645 (6%) developed severe ICH. There was a greater mean hypoxemia burden for infants with severe ICH (3%) compared to those without (0.1%) and remained significant when controlling for multiple confounding factors. Conclusion:: The severe hypoxemia burden in the first week of life is strongly associated with severe ICH.