The hypothalamic-pituitary-adrenal axis is characterized by a marked circadian cycle with heightened activity in the morning. This is synchronized to awakening such that free cortisol increases two to three fold in the first thirty to forty five minutes following awakening — the awakening cortisol response. It has been suggested that this activity, by mobilizing energy reserves prepares the body for the metabolic demands of the day. Similar arguments are applied to the cortisol response to psychological challenge. Paradoxically the cortisol response to a psychosocial stressor is abrogated in fasted individuals with low blood glucose. Also cortisol response to a psychosocial stressor is positively correlated to blood glucose levels after glucose load. We examined if the same relationship applies to the awakening cortisol response. There was no correlation between the cortisol response and awakening blood glucose levels. Moreover a group with mean blood glucose at the bottom of the euglycemic range, identified by split at the median for glucose level upon awakening, showed no deficit in cortisol response. Hence the physiology of the awakening response differs to that of a psychological stress response. These data challenge the view that an oxidisable substrate for energy metabolism is permissive for cortisol responses. In addition the present findings do not support a predominantly gluconeogenic role for morning cortisol activation.