Under hypergravity (HG) cerebral oxygenation falls and can result in G-induced loss of consciousness. Near infrared spectroscopy (NIRS) is a promising tool for HG research, but it is not known whether NIRS derived cerebral tissue oxygenation (StO2) parallels changes in cerebral blood flow (CBF) in humans during HG. Measurements of cerebral blood flow velocity (CBFV) by transcranial doppler ultrasonography, StO2, oxy (O2Hb) and deoxyhaemoglobin (HHb) concentration by frequency-domain NIRS were made during exposure of human subjects (n=8; all male) to transient (0.1G/s to peripheral light loss; PLL) and prolonged HG (+2.6Gz plateau for 120 s) using a man-carrying centrifuge. Peripheral light loss was adjudged, subjectively using a ring of LEDs, as a reduction in visual field to 60°. No anti-G protection was worn. Valsalva manoeuvres (VM) were performed before and after HG exposures as well as during a second +2.6Gz exposure to provide a further haemodynamic challenge. SaO2 was recorded by pulse oximetry and mean arterial pressure (MAP) was non-invasively monitored throughout. Values are means ± S.D., compared by repeated measures ANOVA and Pearson’s r. CBFV and StO2 fell (p<0.001) from 54.5 ±11.4 cm/s and 73 ±4.5 % respectively, to 33.1 (±7.7) and 69 (±3.9) % at PLL, related to a reduction in O2Hb (4.5 ± 2.4 μm/l), rather than a rise in HHb (0.7 ±0.5 μm/l). StO2 and O2Hb changes were highly correlated to CBFV (r=0.80 and r=0.67; p<0.001) when normalised to baseline. During the VM, StO2 and O2Hb changed in concert with CBFV. Although absolute measurements of CBFV and MAP were lower during VM at HG, the response (%Δ from baseline) was unchanged from pre and post values. ΔStO2, however, was lower (p<0.001) due to a larger ΔHHb (p<0.05). ΔHHb tended also to be higher during VM post HG (p=0.054). CBFV fell (n=7) during initial onset of +2.6Gz exposure but remained unchanged at end of +Gz plateau (40.4 ±7.2 cm/s vs 37.4 ±8.8; n.s.), whereas StO2 fell (70.1 ±4.7 vs 65.2±5.2; p<0.01) related to an increase in HHb (+2.4 ±0.7 μm/l; p<0.001) rather than a fall in O2Hb (-1.4 ±1.3 μm/l; n.s.). During short duration HG, StO2 decline is predominately caused by a fall in O2Hb indicative of a reduction in CBF. Further decreases in StO2 when HG is maintained appear to be caused by other mechanism/s. We speculate that increased venous-arterial-blood volume ratio in the measured tissue volume, secondary to either cerebral vasodilatation or increased resistance to outflow from the brain, may be the causative mechanism. These findings highlight complexities in interpreting NIRS data, particularly when only an index of oxygenation is provided.