Objective Critical congenital heart disease (CHD) is associated with neuropsychiatric impairment that may stem from altered cerebral hemodynamics. While cerebral hemodynamics are shown to differ in neonates with CHD, the effect of CHD on cerebral physiology earlier in life during the fetal to neonatal transition period is yet to be elucidated. This period of neonatal resuscitation could represent an opportunity for intervention in critical CHD, so we aimed to characterize cerebral physiology immediately after birth in neonates with critical CHD using noninvasive optical monitoring. Methods This case series analysis included term neonates with hypoplastic left heart syndrome (HLHS; n=2) and with transposition of the great arteries (TGA; n=2) who were born at Children's Hospital of Philadelphia. Continuous measurements of cerebral hemodynamics were acquired during the first hour after birth with novel non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS), as well as commercial near-infrared spectroscopy (NIRS). NIRS measures cerebral oxygenation, and the combined FD-DOS/DCS device measures cerebral oxygenation, blood flow, and metabolism. Results In all four patients, cerebral oxygen saturation was lower than reference values in the literature. Additionally, we observed decreases in cerebral blood flow and oxygen metabolism during postnatal transition that were not reflected by peripheral oxygen saturation. The decreases were spontaneous in infants with HLHS and temporally associated with invasive respiratory support in infants with TGA. Conclusion This study demonstrates periods of neurological vulnerability during postnatal transition in CHD and motivates further research on the use of noninvasive optical monitoring during neonatal resuscitation.