Objective To investigate the expression of double-stranded DNA (dsDNA), citrulline histone 3 (CitH3), myeloperoxidase-DNA (MPO-DNA), IL-8 and IL-33 in plasma of patients with chronic obstructive pulmonary disease (COPD) and their clinical significance. Methods Forty patients with acute exacerbation COPD (AECOPD) who were hospitalized in The First Affiliated Hospital of Shihezi University School of Medicine from October 2020 to May 2021 were recruited in the AECOPD group, and recruited in the stable COPD group when they entered the stable stage. In the same period, forty healthy individuals were recruited in the control group. General informations including pulmonary function and peripheral blood were collected from each subject. Plasma levels of CitH3, MPO-DNA, interleukin (IL)-8 and IL-33 were measured by enzyme linked immunosorbent assay and plasma levels of dsDNA were measured by PicoGreen fluorescent dye quantitative analysis. Results The levels of dsDNA, CitH3, MPO-DNA, IL-8 and IL-33 in the AECOPD group were higher than those in the stable group and the control group, with statistical significance (P<0.05), and the levels of dsDNA, CitH3, MPO-DNA and IL-33 in the stable group were higher than those in the control group, with statistical significance (P<0.05) . The levels of CitH3, MPO-DNA, IL-33 and IL-8 in the AECOPD group were positively correlated with COPD assessment test (CAT) score. MPO-DNA and IL-8 were positively correlated with CAT score, MPO-DNA was negatively correlated with FEV1%pred, CitH3 was negatively correlated with FEV1/FVC. The levels of IL-8 and dsDNA, CitH3 were positively correlated with the levels of MPO-DNA in the AECOPD group, and positively correlated with the levels of IL-8 and dsDNA in the stable group, but not with CitH3 and MPO-DNA. The levels of IL-33 and IL-8, dsDNA, CitH3, MPO-DNA were positively correlated in the AECOPD group, but not in the stable group. Conclusions The levels of neutrophil extracellular traps (NETs), IL-8 and IL-33 in plasma of COPD patients were increased, and the levels of NETs were correlated with pulmonary function, CAT score, IL-33 and IL-8. NETs may be involved in the development of COPD.