INTRODUCTION: Dyspnea and lightheadedness are debilitating symptoms experienced by POTS patients, yet there is paucity of data on their pathophysiology. Invasive cardiopulmonary exercise testing (iCPET) is a novel investigation which gathers physiologic data and better characterizes these phenomena. RESEARCH QUESTION: What is the prevalence of dysfunctional breathing (DB) and preload insufficiency (PI) in POTS patients who undergo iCPET? METHODS: We studied hemodynamics in a cohort of 35 POTS patients who underwent iCPET in a sitting bicycle. The protocol augments CPET with continuous data from pulmonary artery catheterization and arterial line. PI is defined as abnormally low right atrial pressure during exercise and reduced peak cardiac output percentage of predicted. DB is characterized by exercise-induced oscillatory ventilation. RESULTS: The study cohort had a mean age of 40.4 years, and 26 of the 35 patients (74.3%) were female. iCPET revealed the prevalence of only DB as 5.7%, only PI as 37.1%, both DB and PI as 37.1%, and neither DB nor PI as 20% (p=0.006). These 4 sub-groups were then compared for analysis. Notably, the cardiac output percentage of predicted at peak exercise was significantly different between the 4 groups (91.6%, 81.1%, 89.5%, 117.4%; p=0.011). The DB alone subgroup had mean PETCO2 at peak exercise of 28.5, mean VE/VCO2 at AT of 37.5, mean respiratory rate of 39.5 cpm and mean maximal ventilation during exercise of 93.7L. DB was more common in older individuals, while PI was more common in younger individuals (p=0.004). Our study suggests that PI and DB are common entities in POTS with distinct hemodynamic characteristics, and may co-occur. CONCLUSION: This study is a first step towards elucidating various physiological abnormalities in POTS, where symptoms are often debilitating. iCPET yields hemodynamic information that may provide avenues for targeted interventions that could significantly improve quality of life.