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Background: It has been suggested that the deterioration in the antioxidant defense system due to thiols may cause the pro-oxidant/antioxidant imbalance seen in rheumatoid arthritis (RA). This study was conducted to evaluate thiol/disulfide (-SH/-SS) homeostasis in patients with RA compared to healthy controls, and to validate the limited number of studies examining the relationship between Disease Activity Score-28 (DAS28) and thiol parameters., Method: A total of 100 individuals (mean age: 46.3 ± 12.03) consisting of 86 females and 14 males were included in the RA group, and a total of 100 individuals (mean age: 43.3 ± 10.96 years) consisting of 78 females and 22 males were included in the control group. DAS28 was used to assess RA disease activity. -SH/-SS homeostasis parameters were measured using the automated spectrophotometric method described by Erel and Neselioğlu., Results: While native thiol (-SH) (p:0.001), total thiol (-SH + -SS) (p < 0.0001) levels and -SH\(-SS + -SH) ratio (p: 0.018) were lower in the RA group compared to the healthy controls, disulfide (-SS) level (p: 0.005)), -SS\-SH (p: 0.001) and -SS\(-SS + -SH) (p: 0.002) ratios were found to be higher. In the control group and the group in remission (defined by DAS28 < 2.6), the median values of -SH (p:0.002) and -SS + -SH (p:0.0008) were found to be significantly higher, and the median value of -SS (p: 0.001) was found to be lower compared to the other DAS28 groups. While a negative correlation was found between DAS28 and -SH (r: -0.243, p: 0.007), a positive correlation was found between DAS28 and -SS (r: 0.316, p: 0.0003), -SS\-SH (r:0.229, p: 0.002) and -SS\(-SS + -SH) (r: 0.285, p: 0.0009)., Conclusions: The plasma thiol antioxidant pool was decreased in RA compared to healthy controls and those with active disease compared to those in remission., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)