Objective <p>Schizophrenia is a long-term, serious mental health condition that affects thinking, emotions, and behavioral patterns. This study is the first study to investigate calprotectin levels and novel inflammatory indices such as NLR, PLR, SII, SIRI, and PIV in patients with schizophrenia.</p> Methods <p>This prospective case–control study involved 33 individuals diagnosed in patients with schizophrenia and 50 healthy participants. The research was conducted in accordance with the Helsinki Declaration, with informed consent obtained from all subjects. The blood parameters assessed included neutrophil, lymphocyte, platelet, and monocyte levels. Calprotectin concentrations were analyzed using an enzyme-linked immunosorbent assay (ELISA). </p> Results <p>Inflammatory indices, including SII, SIRI, NLR, and PLR, varied significantly between the study groups (p &lt; 0.001). However, no significant differences were observed in monocyte, platelet, and PIV levels (p &gt; 0.05). Calprotectin levels also showed a statistically significant difference between the groups (p &lt; 0.001). The area under curve (AUC) of the calprotectin score for schizoprenia was 0.963.</p> Conclusion <p>These results suggest that SII, SIRI, NLR and calprotectin could serve as reliable biomarkers for monitoring treatment response, and potentially predicting clinical outcomes in patients with schizophrenia.</p>