Introduction: Magnesium sulfate (MgSO4) is frequently administered for maternal and fetal neuroprotection in preeclampsia (PE) and imminent preterm birth, respectively. Objective: To assess whether MgSO4 affects neonatal cerebral oxygenation, blood flow, and cerebral autoregulation (CAR) during the first postnatal days independently from PE. Methods: 148 neonates <32 weeks gestational age were included. Cerebral fractional tissue oxygen extraction (cFTOE) was extracted from a daily 2-h period, during which peak systolic blood flow velocity (PSV) and resistance index (RI) of the pericallosal artery were obtained. The percent time of impaired CAR (correlation coefficient between mean arterial blood pressure and cerebral oxygen saturation >0.5) was determined. Linear mixed models were applied. Results: MgSO4 exposure was recorded in 77 neonates. Twenty-nine neonates were born following PE. MgSO4 independently lowered cFTOE (B: -0.026, 95% CI: -0.050 to 0.002, p < 0.05) but did not affect PSV and RI. PE was associated with a lower cFTOE (B: -0.041, 95% CI: -0.067 to -0.015, p < 0.05) and a tendency towards both lower PSV (B: -4.285, 95% CI: -9.067 to 0.497, p < 0.1) and more impaired CAR (B: 4.042, 95% CI: -0.028 to 8.112, p < 0.1), which seemed to be strongly mediated by fetal brain sparing. MgSO4 did not alter CAR. Conclusions: In contrast to fetal brain sparing in PE, MgSO4 seems to lower cFTOE by lowering cerebral oxygen demands in preterm neonates without affecting the cerebrovasculature.