Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is believed to be a valid biological marker of stress. This study evaluating changes in patients with temporomandibular disorders (TMD) and low back pain (LBP) to determine whether dysregulation of this system represents a marker for chronicity. Salivary cortisol samples were collected from 78 patients (TMD = 41, LBP = 37) upon waking up and 20 minutes later daily for 2 weeks. High-risk patients for chronic pain had different overall cortisol levels versus low-risk patients. High-risk patients exhibited greater variability in terms of cortisol secretion compared with low-risk patients, F(1, 1,243) = 17.73, p <.000. These results provide evidence of a neuroendocrine mechanism underlying a constellation of psychosocial risk factors for chronic pain.