Objectives: We aimed to determine thiol-disulphide homeostasis, which plays a vital role and to investigatethe relationship among homeostatic parameters and disease.Methods: In this prospective study, we enrolled 38 patients with osteoarthritis (31 females and 7 males) and38 healthy controls (30 females, 8 males volunteers). Diagnosis of osteoarthritis was made according to theAmerican College of Rheumatology Criteria. The severity of osteoarthritis was assessed and classifiedaccording to the Kellgren-Lawrence grading scale.Results: The mean age was 63.8 (range; 53-74) years in the osteoarthritis group and 65.6 (range; 55-75) yearsin the control group. There were no significant differences between the patients and controls in respect to age,gender and body mass index (p > 0.05). Serum albumin (p = 0.605) and total protein levels (p = 0.605) betweenpatients and controls were similar. In the osteoarthritis group disulphide/ native thiol percent ratios anddisulphide/ total thiol percent ratios were found to be statistically higher (p = 0.002 and p = 0.002; respectively)and native/ total thiol percent ratios were significantly lower than that of the control group (p = 0.002).Conclusions: Thiol-disulphide homeostasis is weakened in osteoarthritis, and the balance shifts to thedisulphide bond formation side. Substitution of thiol deficiency and correction of thioldisulphide imbalancemay be beneficial in the managing treatment of the disease. Further studies may be needed for evaluatingarticular fluid thiol-disulphide homeostasis.