Objective: To evaluate the effects of diarrhea on appetite among Peruvian children age 12 to 71 months and to assess whether elevated plasma levels of peptide YY, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β contribute to anorexia in this population. Study design: A total of 46 Peruvian children with diarrhea and 46 healthy controls underwent an observed feeding trial that was repeated when cases were healthy. Blood samples were obtained from 30 cases and 30 controls at the first trial and from 30 cases at the second trial and assayed for peptide YY, TNF-α, and IL-1β. Results: In the cases, mean consumption was less when sick than when healthy. The mean plasma level of peptide YY was higher for cases than controls and higher for cases when sick than when healthy. TNF-α levels were higher in cases than controls at visit 1 and also higher in cases when sick than when healthy. There were no differences in IL-1β levels between cases and controls or between cases when sick and healthy. Peptide YY levels in children with diarrhea correlated with the likelihood of them eating less when sick than when healthy. Conclusions: Elevated serum peptide YY may be a mechanism for anorexia in children with diarrhea. © 2008 Mosby, Inc.