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Immunological mechanisms may play a role in symptomatology of patients with a psychotic disorder. Besides metabolic problems and medication use, inflammatory processes that may occur due to the disorder may cause increased inflammatory markers and concurrent psychiatric symptoms. The aim of this study is to investigate whether levels of C-reactive protein (CRP) and white blood cell count (WBC) are related to positive and negative symptoms of psychotic disorders, and whether age, gender, duration of illness, smoking behavior, haloperidol equivalents, mediation use, body mass, and metabolic syndrome affect this relation.CRP and WBC values of 2123 patients with a psychotic disorder were related to positive and negative symptoms measured with a psychiatric interview. CRP was analyzed by survival analysis accounting for detection limit and WBC by linear mixed model analysis. In case of a significant association, the confounding factors were added to the model.Both WBC and CRP were related to both positive and negative symptoms, even after correction for age, gender, smoking, use of medication and metabolic problems. Of the covariates, gender, metabolic problems, smoking and statins also showed a strong association with inflammatory markers.This study in a large patient-group confirmed that inflammatory markers are related to psychotic disorders, particularly negative symptoms. Future studies could use more precise measures of inflammatory markers and measure symptomatic state at specific moments in illness progression.Both positive and negative symptoms are related to WBC and CRP levels.The effects stay when correcting for confounders.Gender, smoking and metabolic problems are also related to inflammatory markers.