OBJECTIVE: The goal was to test the hypothesis that extremes of PaCO2 during the first 4 days after birth are associated with severe intraventricular hemorrhage (grades 3 and 4). METHODS: A single-center retrospective review of clinical and blood gas data in the first 4 postnatal days for 849 infants with birth weights of 401 to 1250 g was performed. The univariate and multivariate relationships of severe intraventricular hemorrhage with maximal and minimal PaCO2, PaCO2 averaged over time (time-weighted PaCO2), and measures of PaCO2 fluctuation (SD of PaCO2 and difference in PaCO2 [maximum minus minimum]) were assessed. RESULTS: Birth weight (mean +/- SD) was 848 +/- 212 g, and the median gestational age was 26 weeks. Infants with severe intraventricular hemorrhage had higher maximal PaCO2 (median: 72 vs 59 mm Hg) and time-weighted PaCO2 (mean: 49 vs 47 mm Hg) values but lower minimal PaCO2 values (32 vs 37 mm Hg). High PaCO2, low PaCO2, SD of PaCO2, and difference in PaCO2 predicted severe intraventricular hemorrhage, but time-weighted average PaCO2 was not as predictive. CONCLUSIONS: Both extremes and fluctuations of PaCO2 are associated with severe intraventricular hemorrhage. It may be prudent to avoid extreme hypocapnia and hypercapnia during the period of risk for intraventricular hemorrhage.