Military divers often operate in cold water eliciting reductions in skin and core temperatures despite the use of thermal protection. Decreases in body temperatures triggers shivering and non-shivering thermogenesis, the latter of which is largely due to the activation of brown adipose tissue (BAT). Ten days of cool air exposure (15-16°C) and seven days of cold-water exposure (14°C) augments non-shivering thermogenesis. However, it is unknown if repeated exposure to cool head out water immersion (CWI) modifies non-shivering thermogenesis. This study tested the hypothesis that fourteen days of CWI for 4 h/d will increase BAT activation. Healthy adults were randomly assigned to either CWI (n=10, 5 women) or thermoneutral head out water immersion (35°C, TNW, n=9, 5 women). CWI and TNW exposures were 4 h in duration and were completed once daily for 14 d in a 16-d period. CWI consisted of the initial immersion in 28°C water and following a 0.5°C reduction in rectal temperature, the water temperature was increased to up to 30°C so that a mild hypothermic state was maintained during the 4 h. Rectal temperature, oxygen uptake (indirect calorimetry), and supraclavicular and trapezius skin temperatures (thermocouples) were measured preexposure and during the middle 3 h of immersion. This analysis was a part of a larger study. Therefore, during the 3 h period, all participants were exposed to hypoxia (FiO2: 0.14). The supraclavicular-trapezius skin temperature difference (Tsk diff) provided an index of BAT activation. Data collected on Day 1 and Day 14 are presented (mean ± SD). Peak decreases in rectal temperature from preexposure were greater in CWI (-0.7±0.3°C) vs. TNW (-0.2±0.4°C, p<0.001) and did not differ between Day 1 and Day 14 in either group (p=0.923). Average oxygen uptake was higher in CWI (0.54±0.09 L/min) vs. TNW (0.38±0.12 L/min, p<0.001) and did not differ between Day 1 and Day 14 in either group (p=0.443). Average Tsk diff did not differ between groups (CWI: 2.2±0.8°C, TNW: 1.6±0.1.1°C, p=0.090) and did not differ between Day 1 and Day 14 in either group (p=0.111). Peak decreases in rectal temperature were significantly correlated with average oxygen uptake (r=-0.552, p<0.001) but not average Tsk diff (r=-0.152, p=0.362). Fourteen days of CWI did not modify thermogenesis (oxygen uptake) nor BAT activation, as estimated from Tsk diff. However, a potential interaction between moderate hypoxia and BAT activation during CWI cannot be excluded. Future work is required to determine the effect of mild hypothermia, such as that experienced by divers operating in cold water even with thermal protection, on more direct markers of BAT activation. Funding: Offce of Naval Research (N00014-20-1-2593 & N00014-21-1-2276). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.