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 has been evidence suggesting dysfunction of small nerve fibres as an underlying pathomechanism. 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 Neurophysiology department to assess small nerve fibre involvement in this group of patients. As microneurography has been incorporated as a clinical service, this opened the opportunity to acquire new insights into the function of peripheral C-nociceptors and sympathetic fibres and their role into potential POTS pathomechanisms.