Recent research highlights inflammation's pivotal role in the etiology of psychotic disorders, emphasizing the potential of inflammatory markers as diagnostic and prognostic tools. This study aimed to elucidate the differential profiles of neutrophil-to-lymphocyte ratio(NLR), monocyte-to-lymphocyte ratio(MLR), platelet-to-lymphocyte ratio(PLR), and systemic immune-inflammatory index(SII) in schizophrenia versus acute psychosis. Conducting a retrospective analysis, we included 126 patients from Prof. Dr. Alexandru Obregia Hospital in Bucharest, divided into two cohorts: 67 patients diagnosed with chronic schizophrenia and 59 with acute psychosis. We extracted complete blood count parameters including white blood cells, neutrophils, monocytes, lymphocytes, and platelets from patient records to compute the NLR, MLR, PLR, and SII indices. Our analysis demonstrated significantly elevated levels of all inflammatory markers in the schizophrenia group, indicating a heightened inflammatory state in the schizophrenia group, with NLR (p < 0.001), MLR (p < 0.05), PLR (p < 0.05), and SII index (p < 0.001)compared to the acute psychosis group. Notably, the schizophrenia cohort exhibited significantly increased NLR, MLR, PLR, and SII indices, suggesting a pronounced systemic inflammatory response in chronic psychotic pathology. These findings underscore the relevance of inflammatory markers in distinguishing schizophrenia from acute psychotic episodes, offering insights into the systemic inflammation's role in the pathophysiology of psychotic disorders. The elevated inflammatory markers in schizophrenia may reflect underlying pathogenetic mechanisms, offering potential targets for novel therapeutic interventions. This study contributes to the nuanced understanding of inflammation's role in psychotic disorders, advocating for further research into inflammatory biomarkers as tools for clinical assessment and management.