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Background: Schizophrenia is a complex neuropsychiatric disorder whose pathophysiology may involve oxidative stress–induced neuronal damage and inflammation. We conducted a cross-species study to elucidate oxidative stress dysregulation in schizophrenia. Methods: We measured peripheral oxidative markers (malondialdehyde [MDA], nitric oxide [NO], reduced glutathione [GSH], superoxide dismutase [SOD], catalase [CAT], advanced protein oxidation products [APOP]) and C-reactive protein (CRP) in antipsychotic-naïve schizophrenia patients and matched controls. We also assayed liver enzymes (ALP, ALT, AST) as indicators of systemic metabolic stress. In parallel, we re-analyzed published single-cell RNA-sequencing data from a Setd1a^+/–^ mouse model of schizophrenia [1] }, focusing on prefrontal cortex (PFC) cell types and oxidative stress–related gene expression. Results: Patients with schizophrenia showed markedly elevated MDA and NO (indicators of lipid and nitrosative stress) and significantly reduced antioxidant defenses (GSH, SOD, CAT) versus controls (p<0.01 for all comparisons). Notably, urban patients exhibited higher oxidative marker levels than rural patients, implicating environmental contributions. Liver function tests revealed increased ALT, AST, and ALP in schizophrenia, suggesting hepatic/ metabolic dysregulation. Single-cell analysis confirmed dysregulated redox pathways in the schizophrenia model: PFC neurons from Setd1a^+/–^ mice displayed significantly lower expression of key antioxidant genes (e.g. Gpx4, Nfe2l2) compared to wild-type, indicating impaired glutathione metabolism. Conclusions: Our integrative data identify convergent oxidative stress imbalances in schizophrenia across species. The findings advance mechanistic understanding of schizophrenia as a disorder of redox dysregulation and inflammation. They also have translational implications: augmenting antioxidant defenses (for example, with Nacetylcysteine or vitamins C/E) could mitigate oxidative injury and neuroinflammation in schizophrenia, representing a promising adjunct to antipsychotic therapy.