OBJECTIVE: In this study, we aimed to study copper metabolism in schizophrenia, bipolar disorder, major depression compared with healthy control. METHODS: This is a single-centered cross-sectional study. The patients with schizophrenia (n = 36), bipolar disorder (n = 37), major depression (n = 40), and healthy control (n = 32) were included in the study. All participants were initially evaluated by a clinical psychiatrist to confirm the appropriate diagnosis using the Structured Clinical Interview for Diagnostic and Statistical Manuel of Mental Disorders-IV (DSM-IV) Axis I Disorders (SCID-I). Serum copper level, ceruloplasmin mass, and ceruloplasmin-ferroxidase activity were measured. One-way ANOVA and Kruskal-Wallis Tests were performed for statistical analyses. RESULTS: Serum ceruloplasmin-ferroxidase activity (chi(2) = 9.11, p = 0.028) demonstrated a significant statistical difference in all groups compared with the control group. Serum ceruloplasmin-ferroxidase activity of the bipolar disorder group was significantly higher than the healthy control group (p = 0.012), major depression group (p = 0.027), and the schizophrenia group (p = 0.019). Erythrocyte sedimentation rate (ESR) (p = 0.028) and waist circumference (p = 0.005) in bipolar disorder group, and the C-reactive protein (CRP) (p < 0.001) and cholesterol (p = 0.043) in the schizophrenia group were found as the determinants of ceruloplasmin-ferroxidase activity. CONCLUSION: In this study, ceruloplasmin-ferroxidase activity is higher in all groups in comparison to the healthy control. The significantly higher ceruloplasmin-ferroxidase activity was shown in bipolar disorder followed by the major depression and schizophrenia. The ceruloplasmin-ferroxidase activity was correlated with erythrocyte sedimentation rate in the bipolar disorder group and with C-reactive protein in the schizophrenia group. Therefore, the ceruloplasmin-ferroxidase activity may be an encouraging candidate in the neuro-immune modulation and become a reliable clinical tool for demonstrating the strong association of inflammation in these disorders.