In order to determine the required duration of whole-body exposure to extreme cold (−110 °C) in males and females for achieving the same cold-induced response, a mathematical model of skin cooling kinetics was developed. This modeling is derived from the implementation of a new experimental cryotherapy protocol to obtain continuous skin temperature maps over time. Each 3-min whole-body cryostimulation session was divided into six incremental sessions of 30 s carried out over six consecutive days. Seventeen young, healthy subjects (8 males aged 22.6 ±3.0 years and 9 females aged 23.7 ±4.7 years) agreed to participate in this study. The smallest sex-related difference in temperature was found in the trunk area (2.93 °C after 3 min) while the greatest temperature drop was found in the lower limbs (5.92 °C after 3 min). The largest temperature variation was observed between the trunk and the lower limbs, and peaked at 2.67 °C in males and 6.99 °C in females. For both sexes, skin cooling kinetics showed a strong transient exponential type decrease followed by linear regression behavior. It appeared that for achieving the same cold-induced response, the required duration of cryostimulation is longer for males. For example, a trunk skin cooling of −12 °C could be achieved in 125s for females vs 170s for males (+36% longer); for the lower limbs, the same skin cooling magnitude could be reached after 87s for females vs 140s for males (+62% longer).