Near Infrared Spectroscopy (NIRS) is an emerging technique for brain oxygenation monitoring in newborns complicated by acute and chronic hypoxia. However, data regarding cerebral oxygenation normal values are still lacking and matter of debate. Therefore, we investigate whether NIRS parameters in healthy preterm/term infants are gestational age and delivery modalities dependent and correlated with standard monitoring parameters. From January to December 2007, 100 healthy newborns with gestational age from 30 to 42 weeks gestation were evaluated. Routine laboratory variables, daily clinical and neurological evaluation and ultrasound imaging were performed. The regional cerebral oxygen saturation (rSO2) and fractional cerebral tissue oxygen extraction (FTOE) were measured by NIRS in the first 6- hours after birth. Data were recorded by MetaVision ICU X-Edition software and analyzed by SPSS statistical package. rSO2 and FTOE correlated (R=-0.77; R=0.41; P < 0.01, for both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P < 0.001, for all) were found at 30-33 wks when compared with other monitoring periods. From 34 wks onwards, rSO2 progressively decreased and FTOE increased reaching their lower dip/peak (P < 0.001, for all) at 38-39 weeks. rSO2 and FTOE values were significantly different (P < 0.05, for both) between preterm and term newborns when corrected for delivery modality. rSO2 correlated (P < 0.001 for all) with heart (r=0.63), respiratory (r=-0.58) rate, and with arterial oxygen saturation (r=0.65). In conclusion, in the first 6-hours after birth cerebral oxygenation in healthy newborns is gestational age-dependent and correlated with routine parameters. NIRS reference curve could be particularly useful in sick newborns brain monitoring.