Patients receiving therapy with hydrocortisone often report that this drug produces stimulant‐like effects or feelings of well‐being. However, little is known about the mood‐elevating effects of hydrocortisone after acute administration. Four healthy volunteers (two men and two women) received intravenous doses of hydrocortisone (0, 25, 50, 100 or 200 mg) on five separate sessions. Plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were obtained, vital signs were monitored, and subjects completed a series of standardized subjective effects questionnaires. Despite large increases in circulating levels of cortisol, hydrocortisone did not produce any detectable stimulant‐like effect on mood or vital signs. To the contrary, hydrocortisone had a mild sedative‐like effect, decreasing ‘arousal’. These preliminary data indicate that acute increases in cortisol do not have either subjective stimulant‐like or mood‐elevating effects.