OBJECTIVE: Postural orthostatic tachycardia syndrome (POTS) is a debilitating condition characterized by autonomic dysregulation. Patients with this disorder may experience orthostatic intolerance, palpitations, fatigue, and a wide variety of other symptoms. The neuropathic symptoms of POTS may be caused by small fiber neuropathy (SFN), which is currently diagnosed using skin nerve biopsy. Corneal confocal microscopy (CCM) is an imaging modality that allows visualization of the corneal nerve layer. Our study aimed to determine whether CCM could detect differences in small nerve fiber parameters between POTS patients with and without signs or symptoms of SFN. MATERIALS AND METHODS: CCM was performed on nine patients, along with a neurological examination. Participants were also asked about neuropathic symptoms by a researcher. Based on examination findings and/or reported symptoms, patients were categorized into SFN+ and SFN- groups for comparison. A chart review was conducted to gather demographic data, medications, autonomic testing results, and medical history, including common POTS comorbidities. RESULTS: Comparison of nerve fiber parameters using CCM did not reveal a statistically significant difference between the groups. However, valuable insights were gained regarding the logistics of conducting this type of study in POTS patients, including adapting to challenges and improving coordination between the neurology and ophthalmology departments. CONCLUSIONS: CCM may one day replace skin nerve biopsy as a diagnostic tool for SFN in POTS patients. Although this preliminary analysis did not demonstrate significant findings, likely due to the small sample size, we believe CCM may still have a role in POTS research and could eventually become a diagnostic tool used in autonomic clinics.