Objective: Vital exhaustion (VE) is characterised by unusual fatigue, increased irritability, and a feeling of demoralisation. It has been found a major risk factor for cardiovascular diseases, and one that is independent of subclinical or clinical manifestations of coronary heart disease or lifestyle-related risk factors. Stress-induced alterations in the hypothalamic-pituitary adrenal (HPA) axis and sympathetic nervous system may mediate the link between VE and increased cardiovascular risk. However, no studies have yet assessed both systems simultaneously and in high-risk populations, such as older adults. Methods: A total of 72 older adults (34 women, mean age 61.7 +/- 7.3) who were free of any major physical or mental illnesses filled out the Maastricht Vital Exhaustion Questionnaire (MVEQ) and the Perceived Stress Scale (PSS). To determine cortisol and alpha-amylase, participants collected saliva samples upon awakening, +30 min thereafter, and at 11 am, 3 pm, and 8 pm. Results: Participants with higher VE reported lower perceived stress (beta = 0.515, p < 0.001). Individuals reporting higher VE also exhibited more diminished cortisol concentrations across the day, although only by trend (beta = 0.218, p = 0.092). There was no significant association between VE and diurnal alpha-amylase activity. Moreover, women had lower diurnal cortisol (beta = 0.381, p = 0.004) and alpha-amylase (beta = 0.329, p = 0.011) when compared to men. Conclusions: Our findings provide initial evidence for psychosocial stress to be linked to VE in older adults, while evidence for HPA alterations remains tentative. Future research is warranted to determine whether VE related hypocortisolaemia represents a specific stage of the stress adaptation process that may put individuals at risk for incident cardiovascular diseases.