© 2015, Springer-Verlag Berlin Heidelberg. Purpose: To determine the sex difference in the impact of central venous pressure (CVP) on the pressor response induced by ischemic handgrip exercise. Methods: Twelve young healthy individuals (six males, 25 ± 3 years) performed ischemic handgrip exercise during mild levels of lower body negative pressure (LBNP, −5 mmHg) and during a 10° head-down tilt (HDT) to lower and increase CVP, respectively. The protocol consisted of 3 min of baseline ischemia, followed by 2 min of isometric handgrip exercise at 35 % of maximal voluntary contraction force, and 2 min of post-exercise circulatory occlusion. Mean arterial pressure (MAP) was assessed continuously by finger plethysmography and CVP was estimated from the venous pressure of the non-exercising dependent arm. Results: Baseline CVP was greater during HDT than LBNP (8.4 ± 1.8 vs. 6.5 ± 1.8 mmHg, p < 0.01). MAP was greater during LBNP than HDT throughout the protocol (p = 0.05). During ischemic handgrip exercise, CVP increased in males but not in females (Group × protocol interaction: p = 0.01). A group × condition interaction was also observed for MAP, with males showing a greater MAP during LBNP than HDT (110 ± 2 vs. 103 ± 2 mmHg, p < 0.01). Conclusions: Baseline CVP inversely affected the pressor response to handgrip exercise in all individuals, with a greater MAP response observed during LBNP than HDT. Increase in CVP in males may be due to a greater splanchnic vasoconstrictor response to ischemic handgrip exercise. Therefore, combined baseline CVP and changes in CVP likely contributed to the greater MAP response observed during LBNP in males.