We investigated the effect of head-down bed rest (HDBR) for 14 days on thermoregulatory sweating and cutaneous vasodilation in humans. Fluid intake was ad libitum during HDBR. We induced whole body heating by increasing skin temperature for 1 hour using a water-perfused blanket through which hot water (42°C) was circulated. The experimental room was air-conditioned (27°C, 30-40% relative humidity). We measured skin blood flow (chest and forearm), skin temperatures (chest, upper arm, forearm, thigh, and calf) and tympanic temperature. We also measured sweat rate by the ventilated capsule method where the skin area for measurement was drained by dry air conditioned at 27°C under similar skin temperatures in both trials. We calculated cutaneous vascular conductance (CVC) from the ratio of skin blood flow to mean blood pressure. From tympanic temperature-sweat rate and -CVC relationships, we assessed the threshold temperature and sensitivity as the slope response of variables to a given change in tympanic temperature. HDBR increased the threshold temperature for sweating by 0.31°C (chest) and 0.32°C (forearm) while reduced sensitivity by 40% (chest) and 31% (forearm). HDBR increased the threshold temperature for cutaneous vasodilation, while decreasing sensitivity. HDBR reduced plasma volume by 11%, while unchanged plasma osmolality. The increase in the threshold temperature for sweating correlated with that for cutaneous vasodilation. In conclusion, HDBR attenuated thermoregulatory sweating and cutaneous vasodilation by increasing the threshold temperature and decreasing sensitivity. HDBR increased the threshold temperature for sweating and cutaneous vasodilation by similar magnitudes whereas decreased their sensitivity by different magnitude.