We investigate the optical properties of the brain in 23 neonates in vivo using a frequency domain near-infrared spectroscopy (NIRS). In this study, a calibration procedure is employed to determine the absorption and reduced scattering coefficients with single source-detector separation. The absorption coefficients of the infant foreheads are lower than the values reported in adults. A large intersubject variation in the reduced scattering coefficients is also demonstrated. Furthermore, physiological parameters are derived from the absorption coefficients at two wavelengths (788 and 832 nm). The mean total hemoglobin concentration (THC) is 39.7±9.8 μM and the mean cerebral blood oxygen saturation is 58.7±11.2%. Our preliminary results show that this bedside frequent domain NIRS could provide quantitative optical measurement of the infant brain. © 2005 Society of Photo-Optical Instrumentation Engineers.