Real‐world settings are composed of multiple environmental stressors, yet the majority of research in environmental physiology investigates these stressors in isolation. The brain is central in both behavioural and physiological responses to threatening stimuli and, given its tight metabolic and haemodynamic requirements, is particularly susceptible to environmental stress. We measured cerebral blood flow (CBF, duplex ultrasound), cerebral oxygen delivery (CDO2), oesophageal temperature, and arterial blood gases during exposure to three commonly experienced environmental stressors – heat, cold and hypoxia – in isolation, and in combination. Twelve healthy male subjects (27 ± 11 years) underwent core cooling by 1.0 °C and core heating by 1.5 °C in randomized order at sea‐level; acute hypoxia (PetO2 = 50 mmHg) was imposed at baseline and at each thermal extreme. Core cooling and heating protocols were repeated after 16 ± 4 days residing at 4330m to investigate any interactions with high altitude acclimatization. Cold stress decreased CBF by 20–30% and CDO2 by 12–19% (both p<0.01) irrespective of altitude, whereas heating did not reliably change either CBF or CDO2 (both p>0.08). The increases in CBF with acute hypoxia during thermal stress were appropriate to maintain CDO2 at normothermic, normoxic values. Reaction time was faster and slower by 6–9% with heating and cooling, respectively (both p<0.01), but central (brain) processes were not impaired by any combination of environmental stressors. These findings highlight the powerful influence of core cooling in reducing CDO2. Despite these large reductions in CDO2 with cold stress, gross indices of cognition remained stable.