Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO(2)) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (S(v)O(2)) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO(2) in physiologic units. In addition, microvascular tissue oxygenation (StO(2)) and indices of microvascular CBF (BFI) and CMRO(2) (CMRO(2)(i)) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO(2) were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O(2)/minute per 100 g, respectively. These CBF and CMRO(2) values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Comparison of MRI measurements of global S(v)O(2), CBF, and CMRO(2) with corresponding local DOS/DCS measurements demonstrated strong linear correlations (R(2)=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The results suggest that MRI and optics offer new tools to evaluate cerebral hemodynamics and metabolism in CHD neonates.