© 2021 Wiley-VCH GmbHObjectives: Onychomycosis is the general term to define fungal nail infections that arise from dermatophytes, non-dermatophytic moulds and yeasts. Thiol/disulphide homeostasis is a new indicator of oxidative stress. In this study, we aimed to investigate the role of thiol/disulphide balance in the pathogenesis of onychomycosis. Methods: This cross-sectional study included adult patients with onychomycosis who were admitted to the dermatology department and healthy adult volunteers without any dermatologic or systemic condition. The patients and controls were evaluated in terms of native thiol, total thiol, and disulphide levels, and disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios. The possible association between these parameters and clinical subtypes of onychomycosis and demographic characteristics was also investigated. Results: A total of 52 patients with onychomycosis and 50 healthy subjects were enrolled in the study. The patient group showed lower levels of total thiol, native thiol and native thiol/total thiol ratio, and higher ratios of disulphide/native thiol and disulphide/total thiol. No statistically significant relationship was found between the parameters, clinical subtypes of onychomycosis and demographic characteristics (p >.05). Conclusion: Patients with onychomycosis showed a shifted thiol/disulphide homeostasis towards oxidative stress with a reduction in thiols and an increase in disulphide/native thiol, and disulphide/total thiol ratios. These findings may indicate the role of oxidative stress in the pathogenesis of onychomycosis.