Previous studies have suggested that, during prolonged cold exposure, shivering thermogenesis may gradually be attenuated, supposedly reflecting a state of central fatigue (aka "thermoregulatory fatigue") provoked by extended shivering activity, that precipitates hypothermia. The purpose of this study was to revisit the validity of this notion. Twelve noncold-acclimatized men participated in three ∼10-h sessions, during which they performed repeatedly three 120-min cold-water immersions. To induce discrete amounts of heat-producing thermoeffector output, presumptively leading to distinct levels of fatigue during each session, subjects were submersed, within each session, in either severely (15°C), moderately (20°C), or slightly (28°C) cold water. The cold-induced elevation in thermogenic rate was similar across the three repeated immersions performed within the 15°C (˜130 W･m2) and 20°C (˜100 W･m2) sessions (P ≥ 0.43). In the 28°C-session, the metabolic heat production was augmented by ˜7% in the second and third immersions compared to in the first immersion (P=0.01). No intrasession differences were noted with regards to the body-core cooling rate, the cold-induced drop in skin temperature and forearm cutaneous vascular conductance, or the stress-hormone (salivary α- amylase and cortisol concentrations) and thermoperceptual responses (P>
0.05). The present findings, therefore, demonstrate that the ability to generate heat remains intact during prolonged iterative exposure to a high-heat loss environment in a single day, regardless of the severity of cold stressor. The intermittent application of slight cold stress (i.e., 28°C water) appears to mediate metabolic sensitization, reflecting either the circadian rhythmicity of heat-producing thermoeffector activity, or perhaps the rapid induction of metabolic adaptation.