Postural orthostatic tachycardia syndrome (POTS) is a common autonomic disorder with a heterogeneous clinical presentation. These patients, mainly young women, present with a wide range of symptoms, such as tachycardia, fatigue, pain and dysfunction of multiple body systems (gastrointestinal, urinary, secretomotor, vasomotor, sudomotor). Although the pathophysiology behind POTS is not yet understood, there is evidence suggesting small nerve fibres dysfunction as an underlying mechanism. Microneurography is a minimal invasive technique, which allows single-fibre recordings from peripheral axons in conscious subjects, providing useful information on the evaluation of C-fibres. In recent years, there has been an influx of referrals to the Clinical Neurophysiology department at Kings College London to assess small nerve fibre involvement in this group of patients. The incorporation of microneurography into a clinical service has opened the opportunity to acquire new insights into the role of C-nociceptors and sympathetic fibres in POTS pathophysiology.