BACKGROUND Maintaining adequate blood pressure to ensure proper cerebral blood flow (CBF) during surgery is challenging. Induced mild hypotension, sitting position or unavoidable intra-operative circumstances such as haemorrhage, added to variations in carbon dioxide and oxygen tensions, may influence perfusion. Several of these circumstances may coincide and it is unclear how these may affect CBF. OBJECTIVE To describe the variation in transcranial Doppler and regional cerebral oxygen saturation (rSO2), as a surrogate of CBF, after cardiac preload and gravitational positional changes. DESIGN Observational study. SETTING Operating room at Hospital Clínic de Barcelona. VOLUNTEERS Ten healthy volunteers, white, both sexes. INTERVENTIONS Measurements were performed in the supine, sitting and standing positions during hyperoxia, hypocapnia and hypercapnia protocols and after a Valsalva manoeuvre. MAIN OUTCOME MEASURES Cardiac index (CI), haemodynamic and respiratory variables, maximal and mean velocities (V max, V mean) (transcranial Doppler) and rSO2 were acquired. Results were analysed using a generalised estimating equation technique. RESULTS CI increases more than 16% after a preload challenge were not accompanied by differences in rSO2 or V max − V mean. With positional changes, V mean decreased more than 7% (P = 0.042) from the supine to the seated position. Hyperoxia induced a cerebral rSO2 increase more than 6% (P = 0.0001) with decreases in V max, V mean and CI values more than 3% (P = 0.001, 0.022 and 0.001) in the supine and standing position. During hypocapnia, CI rose more than 20% from supine to seated and standing (P = 0.0001) with a 4.5% decrease in cerebral rSO2 (P = 0.001) and a decrease of V max − V mean more than 24% in all positions (P = 0.001). Hypercapnia increased cerebral rSO2 more than 17% (P = 0.001), V max − V mean more than 30% (P = 0.001) with no changes in CI. After a Valsalva manoeuvre, rSO2 decreased more than 3% in the right hemisphere in the upright position (P = 0.001). V max − V mean decreased more than 10% (P = 0.001) with no changes in CI. CONCLUSION CBF changes in response to cerebral vasoconstriction and vasodilatation were detected with rSO2 and transcranial Doppler in healthy volunteers during cardiac preload and in different body positions. Acute hypercapnia had a greater effect on recorded brain parameters than hypocapnia.