Systemic corticosteroids are a mainstay of treatment for many pediatric medical conditions. Although their impact on the central nervous system has been well-studied in animal models and adults, less is known about such effects in pediatric populations. The current study investigated acute effects of corticosteroids on memory, executive functions, emotion, and behavior in children and adolescents with inflammatory bowel disease (IBD). Patients 8–17 years with IBD (Crohn's disease, CD; ulcerative colitis, UC) on high-dose prednisone (n = 33) and IBD patients in remission off steroids (n = 33) completed standardized neuropsychological tests and behavior rating scales. In the IBD sample as a whole, few steroid effects were found for laboratory cognitive measures, but steroid-treated patients were rated as exhibiting more problems with emotional, and to a lesser extent with cognitive function in daily life. Steroid effects, assessed by laboratory measures and questionnaires, were more prevalent in CD than UC patients; UC patients on steroids sometimes performed better than controls. Sleep disruption also predicted some outcomes, diminishing somewhat the magnitude of the steroid effects. Corticosteroid therapy can have acute effects on cognition, emotion, and behavior in chronically ill children; the clinical and long-term significance of these effects require further investigation. (JINS, 2012, 19, 1–14)