Cell-free DNA (cfDNA), which is primarily released following cell death, has been described and developed to serve as an effective biomarker in autoimmune diseases which may share the pathogenesis with schizophrenia. In this study, we hypothesized and explored whether the concentrations and size distributions of cfDNA are abnormal in schizophrenia. A total of 65 patients with schizophrenia (SZ), 29 patients with mood disorders (MD) and 62 matched healthy controls (HC) were included in the study. Fluorescence correlation spectroscopy was used to assay the molar concentrations and size distributions of cfDNA. Fluorometric quantification and quantitative real-time PCR (qPCR) were performed to verify the results. The cfDNA levels were approximately two-fold higher in the SZ group ((29 ± 15) nM) than in the healthy controls ((15 ± 9) nM; P-value = 0.00062), but the levels in patients with MD were not significantly different from those in the healthy controls ((17 ± 10) nM; P-value = 0.343). According to the size distribution analysis, cfDNA in schizophrenia patients was composed of shorter DNA molecules and showed an apoptosis-like distribution pattern. Our study shows the elevated levels and short sizes of cfDNA in schizophrenia patients, which provide direct evidences supporting increased apoptotic activity in the disease. cfDNA may be developed to serve as an auxiliary diagnostic marker for the disease in the future.