Adequate oxygen and blood flow are vital for the developing pediatric brain. Herein, we apply quantitative diffuse optical techniques, frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS), to non-invasively characterize cerebral oxygenation (StO2), blood flow (CBF), and oxygen metabolism (CMRO2) in pediatric animal models of hypoxic-ischemic injury. In a neonatal swine model (n=8) of congenital cardiac defect repair, we performed a two-part study which validated non-invasive diffuse optical measurements and uncovered significant limitations in the guidance of deep hypothermia using temperature during cardiopulmonary bypass. First, non-invasive CMRO2 was validated against invasive methods over wide temperature ranges (18-37C). Non-invasive measurements of CBF (p<0.001) and CMRO2 (p<0.001) were significantly associated with invasive measurements. Furthermore, a significant hysteresis (p=0.001) of cerebral metabolic temperature-dependence during cooling versus rewarming with respect to NPT is “fixed” with the use of ICT (p>0.5). Second, we compared non-invasively measured cerebral metabolic parameters between cohorts who underwent deep hypothermia with or without circulatory arrest (DHCA; n=8). Cerebral metabolic temperature-dependence with respect to ICT in DHCA animals demonstrated significantly diminished temperature sensitivity during rewarming (p<0.001; i.e., following reperfusion) compared to during cooling. Direct non-invasive CMRO2 measurement is an improved surrogate of cerebral status over temperature and enables individualized management of deep hypothermia and circulatory arrest. In another study of asphyxia-induced pediatric cardiac arrest and cardiopulmonary resuscitation (CPR), non-invasive measures of StO2, oxy-hemoglobin concentration ([HbO2]) and total hemoglobin concentration (THC) at 10-minutes of CPR were significantly associated with return of spontaneous circulation (ROSC). The absolute change in [HbO2] from 1-minute of CPR ([HbO2]CPR) was the optimal predictor of ROSC, with a mean (SD) AUC of 0.91 (0.07) across the first 10 minutes of CPR, evaluated at 1-minute intervals. Furthermore, separate high sensitivity and specificity threshold for ROSC were established. These results show, in several contexts, that non-invasive FD-DOS/DCS neuromonitoring provides unique physiological information about the developing pediatric brain that enables individualized identification of critical neurological risk periods and real-time guidance of clinical care.