Vasovagal syncope is usually described as a sudden and transient loss of consciousness that resolves spontaneously. Cardiocirculatory changes are well described during and before syncope. However, changes in the cerebral oxygenation are not well defined. In this study, near-infrared spectroscopy (NIRS) was used to assess the cerebral oxygenation directly during 80°head-up (HU) tilt. To simulate central hypovolaemia, 500 ml of blood was drawn from each of 10 healthy subjects. Oxygenation index (OI) was defined as the difference between oxy- and deoxyhaemoglobin concentration. Blood pressure, heart rate and cardiac output were monitored using a finger plethysmographic device. The protocol was divided into two stages, each consisting of a 15-min stabilization period in the supine (SUP) position, 15 min in HU position and another 10 min in SUP position, Between both stages, blood was drawn from the subject. Haemoglobin concentration and haematocrit were measured before and 30 min after withdrawal of blood. No compensatory haemodilution was observed. During HU position in the second stage, six subjects showed signs of presyncope (F) and four did not (NF). A significant difference between F and NF was found in the observation that, before fainting, the OI of F showed a steady and significant (P = 0.02) decrease (-1.4 ± 0.5 $μ$M min-1) compared with NF (-0.18 ± 0.16 $μ$M min-1). This indicates that the onset of (pre)syncope is preceded by a mismatch between oxygen demand and oxygen supply in the cerebrum. Using NIRS enabled us to monitor this mismatch and to predict the onset of a syncope before clear signs in cardiocirculatory variables were visible.