Objectives To determine the acute effect of a mild cold exposure on thermoregulatory thermogenesis and the role of circulating irisin in the process. Methods We studied 22 adults (9 males, 13 females) aged 57.7 ± 10.07 years and body mass index 27.8 ± 4.52 kg/m2. Participants experienced a 90‐min exposure to 20°C and 25°C in a randomized cross‐over design. Resting metabolic rate (RMR), forearm to finger‐tip gradient (FFG), blood pressure (BP), in‐the‐ear temperature (IET), and fasting bloods were measured on each occasion. Results There were significant increases in FFG [mean ± SD: +3.8 ± 3.0°C, P < 0.001], systolic blood pressure (SBP) [+8 ± 13 mm Hg, P = 0.015], and diastolic blood pressure (DBP) [+4 ± 6 mm Hg, P = 0.005] and decreases in IET [−0.24 ± 0.29°C, P = 0.001]. Overall, RMR [+190 ± 570 kJ/d, P = 0.135], irisin, glucose or insulin did not differ between temperatures. There were no significant between‐gender differences, but males significantly increased SBP (+12 ± 16, P = 0.02) and DBP (+6 ± 7, P = 0.02) with decreases in heart rate (−4 ± 3, P = 0.002), while females did not. Moreover men had approximately 50% higher thermogenic response while women had approximately 25% greater vasoconstrictor response. Adjusted for age, gender, insulin sensitivity, and body composition, fold changes in irisin were inversely related to respiratory quotient (r= −0.54, P = 0.048), while IET was related to FFG (r= −0.55, P = 0.043). Conclusions Mild cold exposure increased vasoconstriction with a drop in IET and these were related. Greater irisin was related to a greater fasting fat oxidation in the absence of shivering. A potential gender bias in thermoregulation was noted. Am. J. Hum. Biol. 28:699–704, 2016. © 2016 Wiley Periodicals, Inc.