In the absence of heat stress, females increase blood pressure (BP) during isometric handgrip exercise due to cardiac output more than total peripheral resistance (TPR) compared to men. Although heat stress seems to blunt BP responses at rest and during handgrip, possible sex differences remained unknown. We hypothesized that BP responses during handgrip under a heated environment (HOT) will be different between men and women. Eight healthy men (29 ± 6 years) and eight women (26 ± 4 years) participated in this study. The experimental protocol was separated into two environmental conditions: HOT (~ 36 °C) and thermoneutral (TC; ~ 24 °C). In both conditions, participants rested for 30 min and performed the handgrip for 3 min. BP, heart rate (HR) stroke volume and cardiac output were continuously recorded, and TPR was calculated (TPR = mean blood pressure (MBP)/cardiac output). HOT reduced BP and TPR at baseline and during handgrip in females as compared to TC, while males showed similar responses in both thermal conditions. HR was higher under HOT in both groups. Cardiac output and stroke volume were not different under HOT compared to TC for females. In males, cardiac output increased at the last minute of handgrip under HOT through augmented HR, because stroke volume was unchanged. In conclusion, the main effect of HOT was to shift downwards BP and total peripheral resistance at rest and during isometric exercise in females. In males, the combination of handgrip and HOT increased cardiac output by augmented HR, whereas BP presented similar responses between thermal conditions during handgrip.