The cortisol awakening response: Fact or fiction?

There has been significant discussion in recent years whether the increase in cortisol release that accompanies waking is dependent on the waking process itself or instead reflects a continuation of an underlying circadian rhythm. Establishing the origin or indeed existence of the so-called cortisol awakening response is important as disturbances in post-awakening cortisol secretion are associated with a range of stress-related disorders. The study reviewed in this article adopted an innovative in vivo microdialysis approach to measure tissue-free cortisol levels in 201 healthy volunteers before and after awakening in a home setting (Klaas et al., 2025). Rather surprisingly, the rate of increase in cortisol secretion did not change when participants awoke compared with the preceding hour when participants were asleep. However, considerable between-subject variability was observed, which was partly explained by sleep duration and the timing of waking relative to the previous morning. These findings highlight the complexity of the cortisol awakening response and summon caution in the interpretation of cortisol measurements based solely on post-awakening responses.