Heat-related decreases in cerebral perfusion are partly the result of ventilatory related reductions in arterial carbon dioxide (CO₂) tension. Cerebral perfusion likely contributes to an individual's tolerance to a challenge like lower body negative pressure (LBNP). Thus, increasing cerebral perfusion may prolong LBNP tolerance. This study tested the hypothesis that a hypercapnia-induced increase in cerebral perfusion improves LBNP tolerance in hyperthermic individuals. Eleven individuals (31±7 y; 75±12 kg) underwent passive heat stress (increased intestinal temperature ~1.5°C) followed by a progressive LBNP challenge to tolerance on two separate days (randomized). From 30 mm Hg LBNP, subjects inhaled either (blinded) a hypercapnic gas mixture (5% CO₂, 21% oxygen, balanced nitrogen) or room air (SHAM). LBNP tolerance was quantified via the cumulative stress index (CSI). Mean middle cerebral artery blood velocity (MCAvmean,) and end-tidal CO₂ (P_ETCO₂,) were also measured. 5% CO₂ inhalation increased P_ETCO₂ at ~40 mm Hg LBNP (by 16±4 mmHg) and at LBNP tolerance (by 18±5 mmHg), compared to SHAM (P<0.01). Subsequently, MCAvmean was higher in the 5% CO₂ trial during ~40 mm Hg LBNP (by 21±12 cm.s-1, ~31%) and at LBNP tolerance (by 18±10 cm.s^-1, ~25%) relative to the SHAM (P<0.01). However, hypercapnia-induced increases in MCAvmean did not alter LBNP tolerance (5% CO₂ CSI: 339±155 mm Hg x min; SHAM CSI: 273±158 mm Hg x min; P=0.26). These data indicate that inhaling a hypercapnic gas mixture increases cerebral perfusion during LBNP but does not improve LBNP tolerance when hyperthermic.