Both mucosal inflammation and psychologic dysfunction have been implicated in irritable bowel syndrome (IBS). While some relationships between inflammation (mast cells and eosinophils) and depression have been reported in adults with IBS, relationships between inflammation and psychologic function have not been studied in children and adolescents. The aims of the current study were to: (1) assess densities of colonic mast cells, eosinophils, and TH17 cells in youth with IBS; and, (2) explore relationships between these cells and specific IBS symptoms and psychologic functioning. Utilizing previously obtained biopsies from the descending and rectosigmoid colons, densities were determined for mast cells, eosinophils, and TH17 cells, respectively, in 37 youth with IBS and 10 controls. In IBS patients, densities were assessed in relation to specific IBS symptoms and in relation to self-report anxiety and depression scores. In both the descending and rectosigmoid colons, densities of mast cells, eosinophils, and TH17 cells were higher in IBS patients as compared to controls. In IBS patients, rectosigmoid mast cell density was higher in those reporting pain relief with defecation. Also, in IBS patients, rectosigmoid eosinophilia was associated with higher anxiety scores and eosinophil density correlated with depression scores. In the descending colon, eosinophil and mast cell densities both correlated with depression scores. In conclusion, mucosal inflammation (mast cells and eosinophils) is associated with pain relief with defecation and with anxiety and depression in youth with IBS.