Near-infrared spectroscopy (NIRS) can monitor changes in cerebral regional oxygen saturation (rSO₂) and tissue hemoglobin content (HbT). The relation between cerebral NIRS readings and vital parameters has not been analyzed before at a fine temporal scale. This study analyzed this relation during cardiopulmonary bypass (CPB) surgery in 10 children (0–9 years, 1,770 min of data records) by using a novel random-coefficient model. The analysis indicated that a small number of patients is sufficient for obtaining significant results with this model. Changes of vital parameters explained 84.7 % of rSO₂ changes and 90.7 % of HbT changes. Cerebral rSO₂ correlated positively with perfusion pressure and inversely with body temperature (P < 0.05). Cerebral HbT correlated positively with perfusion pressure, central venous pressure, and temperature and inversely with arterial oxygen saturation (P < 0.05). During hypothermic circulatory arrest, the half-life of the exponential rSO₂ decay correlated to the rSO₂ reserve (P = 0.016). In conclusion, NIRS readings of cerebral hemoglobin content and tissue oxygen saturation correlate well to vital parameters during CPB surgery in children. NIRS may therefore become a monitoring device for the neuroprotective optimization of those vital parameters.