Placental lesions are associated with neurological morbidity but the mechanism leading to morbidity is unclear. To provide insight into such a possible mechanism, we determined whether placental lesions were associated with regional cerebral tissue oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) in preterm infants during their first 5 d after birth. We hypothesized that as a result of cerebral hypoperfusion, rcSO2 would be lower and FTOE would be higher.In a prospective, observational study of 42 preterm infants (gestational age <32 wk), the infants' placentas were examined for histopathology. We measured rcSO2 and transcutaneous arterial oxygen saturation (SpO2) on days 1-5. FTOE was calculated as FTOE = (transcutaneous SpO2 - rcSO2)/transcutaneous SpO2.Only three placentas showed no pathology. Ascending intrauterine infection (AIUI) (n = 16) was associated with lower rcSO2 and higher FTOE values on days 2, 3, and 4 (P ≤ 0.05). Other placental lesions were not associated with rcSO2 and FTOE.AIUI is associated with lower rcSO2, and higher FTOE shortly after birth. The effect it has on cerebral oxygenation might be the mechanism leading to neurodevelopmental problems.