The aim of this paper was to investigate serum concentrations of calcium-independent lipoprotein phospholipase A2 (PLA2) and protein S100 in schizophrenia patients in comparison to healthy controls and correlate them with the clinical severity, duration, and number of schizophrenia relapses. This study included 65 schizophrenia patients and 70 controls. Schizophrenia was diagnosed according to DSM-IV-TR criteria. Clinical severity was determined by PANSS. PLA2 and protein S100 concentration were assessed by the enzyme-linked immunosorbent assay (ELISA). PLA2 concentrations were higher in patients with schizophrenia, whereas protein S100 concentrations were not. Higher concentrations of PLA2 were positively correlated with the duration of illness and number of episodes, as determined by multivariate analysis. PLA2 might be considered a possible biochemical trait marker for schizophrenia. Further research with larger and more homogeneous clinical samples is required.