Objective To investigate oxidative stress parameters [total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), paraoxonase (PON), arylesterase (ARE) and thiol-disulphide homeostasis] in patients who were diagnosed as having somatic symptom disorder in accordance with Diagnostic and Statistical Manual of Mental Disorders-5. Methods The study included 41 medication-free patients with somatic symptom disorder and 47 age, sex, and sociodemographic-matched healthy individuals. The patients were administered the Patient Health Questionnaire-15, Somatic Symptom Amplification Scale, Beck Depression Inventory, and Beck Anxiety Inventory. TOS, TAS, OSI, PON, ARE thiol, disulphide levels, and routine biochemical parameters were compared between the two groups. Results TOS, OSI, disulphide levels, disulphide/native thiol, and disulphide/total thiol ratios were found significantly higher in the patient group compared with the control group (p < 0.001). There was no significant difference in PON, ARE, and TAS parameters between the two groups (p > 0.05). Conclusion This study showed that the level of oxidants increased and oxidative balance was impaired in somatic symptom disorder. Oxidative stress may play a role in the aetiopathogenesis of this disorder. This is the first study to report an association between oxidative stress and somatic symptom disorder.