Previous reports have found low levels of dehydroepiandrosteron sulfate (DHEA-S) in association with frailty in elderly patients. The mechanisms underlying these associations are not known. Therefore, psychiatric symptoms and disorders that are common in frail elderly patients were correlated with DHEA-S levels in a convenience sample selected from a nursing home population. Low DHEA-S levels were associated with high degrees of self-rated disability and insomnia. In women, low DHEA-S levels were also associated with increased numbers of pain sites. However, cognitive impairment was associated with higher DHEA-S levels in women. Thus, in frail elderly patients, there are contradictory relationships between DHEA-S and neuropsychiatric measures of frailty (cognitive impairment, disability, insomnia, and number of pain sites), and ther may also be gender differences in these relationships.