The exact etiology of Postural Orthostatic Tachycardia Syndrome (POTS) is still unknown but is likely heterogeneous and multifaceted, involving autoimmune, neuropathic, hypovolemic, and hyperadrenergic pathways. Recently, more research has been devoted to understanding POTS's underlying immune etiology. We investigated the potential association between elevated levels of prostaglandin chemoattractant receptors (CRTH2) expressed on T-cells and the clinical manifestations observed in patients with POTS. We performed immunophenotyping using flow cytometry on 20 consecutive patients with POTS confirmed by tilt table testing and compared our findings with healthy controls. POTS patients demonstrated an increase in CRTH2 levels on (CD8+) T cells and CD8+/CD45RO+ T cells compared to controls. CRTH2 is expressed significantly on TH2 and CD8+ cells in POTS patients compared with controls. Since CRTH2 mediates the action of mast cell degranulation mediators such as PGD2 on TH2 cells it results in the release of inflammatory cytokines and interleukins that cause vasodilation and cellular inflammation with capillary leak, leading to reduced effective intravascular volume and reduced venous return, which are known as potential mechanisms in the pathophysiology of POTS, we conclude that CRTH2 plays an important role in the pathophysiology of POTS.