Background: Autonomic dysfunction (AD) is a significant problem in primary biliary cirrhosis (PBC) and is equally present in early disease stages. Currently, AD in PBC is considered to be central in origin. The aim of this study was to examine peripheral mechanisms in the pathogenesis of AD in PBC using novel microvascular optical assessments for this patient group. Methods: Twenty‐four early stage PBC patients and 24 age‐matched controls attended for two microvascular optical‐based measurement techniques. Firstly, the regulation of microvascular blood volume to the periphery was assessed using multisite photoplethysmography (PPG) by examining the degree of correlation between the right and left sides of the body, with reduced correlation consistent with peripheral AD. Secondly, the peripheral vasomotor reflex response to standing was dynamically tested using laser Doppler flowmetry to quantify the degree of autonomic tone in peripheral vasoconstriction. Results: PBC patients had a significantly reduced right to left side blood volume multisite PPG correlation compared with controls when corrected for age, body mass index, heart rate and systolic blood pressure [impaired synchronization between pulse wave amplitude between right and left fingers and right and left ears (both P <0.05)]. The veno‐arteriolar reflex on standing in PBC patients was significantly lower than for the controls, consistent with poorer autonomic tone for vasoconstriction in PBC (P <0.01). Conclusions: This study provides evidence for the presence of peripheral autonomic nervous system involvement in PBC. Prospective studies are now warranted to determine the full clinical potential of microvascular optical assessment in PBC.