This study investigates the role of inflammatory markers in perception disorders associated with major psychiatric pathology, focusing on schizophrenia and acute psychotic disorder. Guided by the vulnerability–stress–inflammation model, this research explores how genetic predispositions, maternal immune activation, and chronic low-grade neuroinflammation contribute to disease onset and progression. A sample of 135 patients (69 with schizophrenia and 66 with acute psychotic disorder) admitted to a psychiatric hospital between October 2024 and February 2025 was analyzed. Demographic and clinical data, along with biological markers—such as white blood cells, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)—were assessed. Results indicated elevated median values for SII, CRP, and MLR, with statistically significant differences compared to normal reference ranges, suggesting persistent systemic inflammation in psychotic disorders. While acute psychotic disorders showed wider value ranges, schizophrenia patients demonstrated higher median levels, consistent with chronic inflammation. No significant differences were observed between the two groups after Bonferroni correction, though CRP values suggested a trend toward greater inflammation in schizophrenia. These findings reinforce the inflammatory hypothesis of psychosis and highlight the potential of biomarkers to refine diagnosis, guide treatment strategies, and support future research into immunomodulatory therapies.