Objective: Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. Methods: Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphideative thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global ImpressionSeverity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms. Results: After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups. Conclusion These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia.