Background: Primary Sjögren's syndrome (pSS) is a disease associated with the overexpression of proinflammatory cytokines, and oxidative stress is one of the factors responsible for its etiopathogenesis. This study aimed to investigate the thiol/disulphide homeostasis in pSS patients. Methods: The study included 68 pSS patients and 69 healthy controls. Thiol/disulphide homeostasis (total thiol, native thiol, and disulphide levels) was measured using the automatic spectrophotometric method developed by Erel and Neselioglu, and the results of the 2 groups were compared. Results: The gender and age distributions of the pSS and control groups were similar (P = 0.988 and P = 0.065). Total thiol and native thiol levels were lower in the pSS group than in the control group (470.08 ± 33.65 mmol/L vs. 528.21 ± 44.99 mmol/L, P < 0.001, and 439.14 ± 30.67 mmol/L vs. 497.56 ± 46.70 mmol/L, P < 0.001, respectively). There were no differences in disulphide levels between groups 17.00 (range 0.70-217.0) mmol/L vs. 14.95 (range 2.10-40.10) mmol/L, P = 0.195. Conclusions: It was concluded that the thiol/disulphide balance shifted towards disulphide in patients with pSS.