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Background: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease., Objectives: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged., Methods: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls., Results: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups., Conclusions: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies.