Irritable bowel syndrome (IBS) is one of the most frequently diagnosed disorders, affecting about 20% of the general population in Western countries. This syndrome poses an enormous socio-economic burden, impairs the quality of life substantially, and increases healthcare costs. IBS can be classified as either idiopathic (ID-IBS) with unknown etiology or post-infectious (PI-IBS), which develops after a bout of acute diarrhea or gastroenteritis. Little is known about the immunopathogenesis of these two forms of IBS. We evaluated various biomarkers in clinical samples of ID-IBS and PI-IBS patients with the goal to test the hypothesis that the immunologic presentations of these forms of IBS are similar, despite their apparent different etiologic origins. Sera and stool samples from PI-IBS, ID-IBS, and healthy volunteers were analyzed for relative amounts of 36 different biomarkers using the Proteome Profiler Human Cytokine Array Panel A Kit and quantitative ELISA. Our results demonstrated significantly high levels of chemotactic chemokines monocytes chemotactic protein-1 (CCL2) [p-value  = 0.003], macrophage inflammatory protein-1β (CCL4) [p-value  = 0.010], and CXCL16 (p-value 0.001) in the sera and stools of both ID-IBS and PI-IBS patients. Furthermore, pro-inflammatory cytokines (IFN-γ, IL-1β, and TNF-α) were significantly higher in IBS patients. Anti-inflammatory cytokines (IL-10, IL-4, and IL-13) were variable except IL-10, which was significantly higher in the healthy volunteers than the IBS patients. Remarkably, the amounts and expression pattern of these biomarkers were not significantly different between ID-IBS and PI-IBS. Thus, ID-IBS and PI-IBS present similar immunologic and clinical phenotypes, in spite of their different etiologic origins.