Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina survivors relative to a non-exposed community comparison group. It was hypothesized that Hurricane Katrina survivors would experience lower basal morning cortisol and greater cortisol suppression with low-dose dexamethasone than the comparison group. Methods: Fourteen Hurricane Katrina survivors and nine non-exposed community residents were assessed 21 months after the disaster in this observational pilot study with an experimental component. Salivary cortisol was collected at baseline and following low-dose dexamethasone challenge. Posttraumatic stress disorder (PTSD), depressive, and externalizing symptoms were assessed with self-report instruments. Results: Relative to the community participants, Hurricane Katrina survivors had significantly higher PTSD and depressive symptoms, and, as hypothesized, lower basal morning salivary cortisol. In the full sample, basal morning cortisol was negatively associated with depressive and externalizing symptoms. The hypothesis that low-dose dexamethasone challenge would show more cortisol suppression in Hurricane Katrina survivors than the comparison group was not supported, perhaps reflecting more depressive symptoms in the survivors or due to a floor effect of low cortisol levels. Conclusions: The results augment the extant literature on youth exposed to disasters by emphasizing the importance of depressive and externalizing symptoms as well as PTSD symptoms in HPA axis functioning. Future research is needed to fully elucidate HPA axis functioning in youth exposed to disasters.