Objectives:Evidence has accumulated that men and women show different responses to noxious stimuli, with women exhibiting greater sensitivity to pain than men. Data concerning sex differences in Cortisol response patterns have revealed inconsistent results so far. The purpose of the present study was to examine sex differences in subjective pain and Cortisol response to a noxious stressor.Methods:Seventy‐six subjects (39 male and 37 female) were investigated by a modification of the cold pressor test that consisted of intermittent immersion of the hand into ice water (plunge test, PT). The PT was conducted twice, in consecutive trials, to guarantee a sufficient exposure to the noxious stressor for eliciting Cortisol responses. In each trial, tolerance time and pain ratings visual analog scale (VAS) were assessed. Seven saliva samples (c1‐c7) were collected to determine Cortisol levels at baseline (c1‐c2), directly before (c3) and 20 minutes after noxious stress (c4), and during recovery period (c5‐c7).Results:We found no significant sex differences in tolerance time in trial 1, but highly significant differences in tolerance time in trial 2, with higher tolerance times in men. No significant sex differences were found for the VAS ratings of pain intensity and unpleasantness in the 2 trials. In contrast, a significantly larger Cortisol increase in men was observed compared with women. Analysis of covariance revealed that this result could not be attributed to sex differences in Cortisol level at baseline and in tolerance time.Discussion:The present study demonstrates that men show a larger Cortisol response to a noxious stressor than women that is not attributable to sex differences in subjective pain. The conclusion of a causal relation between larger Cortisol responses and higher pain tolerance thresholds in men is tempting but yet speculative.