BACKGROUND: Inflammation may play an important role in the pathogenesis of schizophrenia and related psychotic disorders. This study aimed to measure the inflammatory marker (serum prolactin, serum cortisol, C-reactive protein [CRP], erythrocyte sedimentation rate (ESR), total leucocyte count, and differential leucocyte count) in drug naïve patients of the first episode of acute and transient psychotic disorder (ATPD) at baseline and their alterations after three months of antipsychotic treatment. METHODS: This prospective study estimated the change of inflammatory biomarkers in patients with ATPD over three months, along with the change in psychopathology and global functioning. Attempts were taken to compare the trend of change in inflammatory biomarkers with clinical improvement. RESULT: A total of 157 patients with ATPD were screened to recruit 78 patients, of which only 33 patients were followed up till three months from the point of recruitment. More than three-fourths of the patients improved significantly during the brief follow-up period. Patients who improved substantially with antipsychotic drug treatment had a significantly lower age and age at the onset of psychiatric illness. The patients who improved also had a significant reduction in total leucocyte count, absolute neutrophil count, and neutrophil-to-lymphocyte ratio from baseline to three-month follow-up. Duration of untreated illness had a significant positive correlation ( CONCLUSION: Inflammatory biomarkers are raised in drug naïve patients with ATPD, which improves with antipsychotic drug treatment, indicating a possible role of inflammation in the pathogenesis of ATPD.