Objective To investigate the expression levels of lysophosphatidic acid (LPA) and soluble ST2 (sST2) in plasma of patients who had COPD and their clinical significance. Methods Forty-two patients with acute exacerbation COPD (AECOPD) who were hospitalized in the First Affiliated Hospital of Shihezi University School of Medicine from October 2021 to June 2022 were selected as the AECOPD group, and recruited in the stable COPD group when they received treatment and entered the stable period. In the same period, forty healthy individuals were recruited in the control group. The general information and peripheral blood were collected from each group. the pulmonary function test was tested in the stable and control group, and the LPA and sST2 levels were measured by enzyme-linked immunosorbent assay. Results The levels of LPA and sST2 in the AECOPD group were higher than those in the stable group, with statistical significance (both P<0.05)，and the levels of LPA and sST2 in the AECOPD group and stable group were higher than those in the control group, with statistical significance (all P<0.05). The levels of LPA in AECOPD group and stable group were both positively correlated with the levels of sST2. The levels of LPA and sST2 in AECOPD group were positively correlated with white blood cell count, neutrophil percentage, red blood cell distribution width, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and albumin, and the levels of LPA in AECOPD group was positively correlated with monocyte-to-high density lipoprotein ratio, the levels of sST2 in AECOPD group was positively correlated with eosinophil count. The levels of LPA and sST2 in COPD group were negatively correlated with FEV1%pred, FEV1/FVC, and were positively correlated with white blood cell count, neutrophil percentage, red blood cell distribution width, and neutrophil-to-lymphocyte ratio. The levels of LPA were positively correlated with platelet-to-lymphocyte ratio, and the levels of sST2 were positively correlated with eosinophil count and albumin. Conclusion The levels of LPA and sST2 in COPD patients were highly expressed, and the levels of LPA were positively correlated with sST2, and they were both correlated with lung function and clinical indicators, suggesting that LPA and sST2 may be both involved in the occurrence and development of COPD