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Objectives: The aim of the study was to assess the relationship between the improvement of the clinical condition of patients with the first episode of psychosis (FEP) and changes in - nitric oxide (NO) plasma concentration based on the level of its metabolites NO2- and NO3, as well as changes in lipid profile and biomarkers of systemic inflammation., Methods: The study was carried out in agroup of 25 young patients with FEP (aged 14-35). Blood samples were collected in the 1st and 12th week after admission to the hospital to assess NO metabolites, lipid profile and inflammatory biomarkers. Demographic and clinical data were also analysed., Results: In the study group, three months after admission to the hospital, an improvement in the clinical symptoms was observed, as evidenced by a decrease in the Positive and Negative Syndrome Scale (PANSS) scores. This improvement was associated with a decrease in the plasma nitrite concentration, a deterioration of the lipid profile and the activation of systemic inflammation. Interestingly, in the 1st week after the hospital admission, a longer duration of untreated psychosis (DUP) was associated with a lower NO2- plasma concentration, and a higher intensity of positive symptoms (PANSS Positive Symptoms Scale) was associated with higher CRP plasma level., Conclusions: Our results suggest that adverse metabolic response, systemic inflammation and a fall in systemic NO bioavailability represent early systemic manifestations of FEP that are not controlled by short-term anti-psychotic treatment and may pose cardiovascular risk.