Brain serotonin 4 receptor binding is associated with the cortisol awakening response

•We performed a cross-sectional study to evaluate the association between brain serotonin 4 receptor binding and HPA-axis dynamics in healthy individuals.•We demonstrate a robust negative association between brain serotonin 4 receptor binding and the cortisol awakening response.•Our results reinforce an association between serotonin signalling and HPA-axis function in the human brain.•We suggest that serotonergic neurotransmission support HPA-axis dynamics in healthy individuals.