Objectives The aim of this study was to determine the extent of autonomic dysfunction in patients with clinically isolated syndrome (CIS) by using a standardized battery of autonomic tests in the form of the Composite Autonomic Scoring Scale (CASS). Methods This was a prospective, cross sectional study which included 24 consecutive patients who were diagnosed with CIS and 17 healthy controls. In all participants, heart rate and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing and blood pressure response to passive tilt were performed. In 16 patients, Quantitative Sudomotor Axon Reflex Test (QSART) and catecholamine measurement was performed. Results The proportion of CIS patients with pathological adrenergic index was statistically significantly higher compared to healthy controls (12 vs 2, p =0.018), while there was no difference in cardiovagal index between groups. Five patients had a sudomotor index of 1 (in 4 there was hypohydrosis <50% and in 1 persistent foot hyperhidrosis). When combining adrenergic, cardiovagal and sudomotor index into CASS, 8 patients (50%) had evidence of autonomic dysfunction, 7 mild and one moderate. Conclusion Sympathetic nervous system is frequently affected in CIS patients. Significance CASS is able to detect autonomic nervous system dysfunction in CIS patients.