Background & aims: Appetite disturbance is an important nutritional issue in Crohn's disease (CD), but the biological basis is unclear. Satiety signals such as polypeptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are produced by enteroendocrine cells (EEC). In animal models, upregulation of EEC plays a mechanistic role in feeding disturbance and weight loss. We recently showed increased EEC activity in tissue from active small bowel CD. This study investigated EEC products in plasma in CD, and appetite-related symptoms. Methodology: Active CD patients and a healthy reference group were studied. Gut peptide responses to a mixed nutrient test meal were measured by ELISA. Symptoms were assessed by visual analogue score. A patient subset was re-studied in remission. Results: CD subjects displayed reduced appetite (p <0.0001) before and after eating. Total PYY was increased 2.2-fold (p = 0.04) and correlated with nausea (p = 0.036) and bloating (p = 0.037) scores only in small bowel CD. Postprandial plasma ghrelin levels were also elevated. Leptin correlated with body mass index (p = 0.0001) and weight loss (p = 0.01). GLP-1 and GIP were not elevated. In remission, postprandial PYY and ghrelin reverted to control levels. Discussion: Enhanced EEC responses may directly and adversely affect appetite in CD patients through increased gut-brain signalling. © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.