<jats:sec><jats:title>New Findings</jats:title><jats:p><jats:list list-type="bullet"> <jats:list-item><jats:p><jats:bold>What is the central question of this study?</jats:bold></jats:p> <jats:p>In acute hypoxia, the reduction in arterial CO<jats:sub>2</jats:sub> tension due to the hypoxic ventilatory response (respiratory chemoreflex) stimulates cerebral vasoconstriction, which opposes the degree of hypoxic cerebral vasodilatation. The aim was to examine this interaction further. Specifically, we questioned whether arterial CO<jats:sub>2</jats:sub> tension‐mediated effects on cerebrovascular regulation are attenuated during acute hypoxia.</jats:p></jats:list-item> <jats:list-item><jats:p><jats:bold>What is the main finding and its importance?</jats:bold></jats:p> <jats:p>Cerebrovascular CO<jats:sub>2</jats:sub> reactivity and CO<jats:sub>2</jats:sub>‐mediated effects on dynamic cerebral autoregulation were attenuated during acute hypoxia. These findings suggest that blunted cerebrovascular responses to CO<jats:sub>2</jats:sub> may limit the degree of CO<jats:sub>2</jats:sub>‐mediated vasoconstriction to help maintain adequate cerebral blood flow for cerebral O<jats:sub>2</jats:sub> homeostasis during acute hypoxia.</jats:p></jats:list-item> </jats:list></jats:p></jats:sec><jats:sec><jats:label /><jats:p>In normoxic conditions, a reduction in arterial carbon dioxide tension causes cerebral vasoconstriction, thereby reducing cerebral blood flow and modifying dynamic cerebral autoregulation (dCA). It is unclear to what extent these effects are altered by acute hypoxia and the associated hypoxic ventilatory response (respiratory chemoreflex). This study tested the hypothesis that acute hypoxia attenuates arterial CO<jats:sub>2</jats:sub> tension‐mediated regulation of cerebral blood flow to help maintain cerebral O<jats:sub>2</jats:sub> homeostasis. Eight subjects performed three randomly assigned respiratory interventions following a resting baseline period, as follows: (1) normoxia (21% O<jats:sub>2</jats:sub>); (2) hypoxia (12% O<jats:sub>2</jats:sub>); and (3) hypoxia with wilful restraint of the respiratory chemoreflex. During each intervention, 0, 2.0, 3.5 or 5.0% CO<jats:sub>2</jats:sub> was sequentially added (8 min stages) to inspired gas mixtures to assess changes in steady‐state cerebrovascular CO<jats:sub>2</jats:sub> reactivity and dCA. During normoxia, the addition of CO<jats:sub>2</jats:sub> increased internal carotid artery blood flow and middle cerebral artery mean blood velocity (MCA <jats:italic>V</jats:italic><jats:sub>mean</jats:sub>), while reducing dCA (change in phase = −0.73 ± 0.22 rad, <jats:italic>P</jats:italic> = 0.005). During acute hypoxia, internal carotid artery blood flow and MCA <jats:italic>V</jats:italic><jats:sub>mean</jats:sub> remained unchanged, but cerebrovascular CO<jats:sub>2</jats:sub> reactivity (internal carotid artery, <jats:italic>P</jats:italic> = 0.003; MCA <jats:italic>V</jats:italic><jats:sub>mean</jats:sub>, <jats:italic>P</jats:italic> = 0.031) and CO<jats:sub>2</jats:sub>‐mediated effects on dCA (<jats:italic>P</jats:italic> = 0.008) were attenuated. The effects of hypoxia were not further altered when the respiratory chemoreflex was restrained. These findings support the hypothesis that arterial CO<jats:sub>2</jats:sub> tension‐mediated effects on the cerebral vasculature are reduced during acute hypoxia. These effects could limit the degree of hypocapnic vasoconstriction and may help to regulate cerebral blood flow and cerebral O<jats:sub>2</jats:sub> homeostasis during acute periods of hypoxia.</jats:p></jats:sec>