Thiol-disulphide homeostasis (TDH) is a new parameter indicating oxidative stress that plays a role in the pathogenesis of various clinical disorders . Our study planned to investigate TDH in COVID-19 patients . Age and gender-matched healthy subjects (n=70) and COVID-19 patients (n=144) were included in the study . In addition to the routine laboratory parameters of the groups, their native thiol (NT), total thiol (TT) and disulphide levels were measured . Primarily, we compared COVID-19 patients to the healthy control group for inflammatory parameters, NT, TT and disulphide levels . Then, COVID-19 patients were divided into two groups according to the severity of the disease as mild to moderate and severe COVID-19, and the three groups were compared with each other . Predictive value of thiol parameters in the diagnosis of COVID-19 and in the determining its severity, and its correlation with presence and duration of symptoms were investigated . Severe COVID-19 patients had lower NT and TT levels compared with healthy controls and mild to moderate patients (P <0.001 for both). The results of ROC analysis show that the greatest AUC was IL-6 and NT (AUC=0.97, AUC=0.96, respectively) between control and COVID-19 patients, while it was CRP and NT (AUC=0.85, AUC=0.83) between mild to moderate and severe patients . A negative correlation was found between duration of symptoms of dyspnoea, cough, fever, and sore throat and NT (r=-0.45, P=0.017, r=-0.418, P <0.001, r=-0.131, P=0.084, r=-0.452, P =0.040, respectively). NT and TT levels have a strong predictive value in the diagnosis of COVID-19 and in determining disease severity . Our results support that changing TDH parameters appears to have an important role in disease pathogenesis and it can be used in clinical management of patients.