Abstract Background The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO 2 ), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO 2 from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m 2 , age 30.8 ± 13.4 years). Results We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO 2 oscillations (textless 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema. Conclusions Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO 2 and SAS width monitoring might be beneficial for patients with acute lung disease.