Objective: To analyze the expression and correlation of serum-soluble myeloid cell trigger receptor-1 (sTREM-1), complement C1q tumor necrosis factor-related protein 5 (CTRP5) and soluble human matrix lysin-2 (sST2) in chronic obstructive pulmonary disease (COPD). Methods: Data were collected from 106 COPD patients admitted to our hospital from January 2019 to January 2020. This observation group was divided into a COPD aggravation group and a COPD stabilization group, according to the patients' disease conditions. During the same period, 40 healthy subjects in the physical examination center of our hospital were selected as a control group. Six milliliters of fasting blood were collected from each subject in the morning, and the serum sTREM-1, CTRP5 and sST2 levels were detected by a double-antibody sandwich enzyme-linked immunosorbent assay. The serum sTREM-1, CTRP5 and sST2 levels of each group of subjects were compared. The Spearman correlation was used to analyze the expression and correlation of serum sTREM-1, CTRP5 and sST2 in COPD. Results: The serum sTREM-1, CTRP5 and sST2 levels in the observation group were significantly higher than those in the control group, and the serum sTREM-1, CTRP5 and sST2 levels in the COPD aggravation group were significantly higher (P< 0.01) than those in the COPD stabilization group. Serum CRP and PCT levels in patients in the COPD aggravation group were markedly higher than those in the COPD stabilization group, and CAT scores in patients in the COPD aggravation group were remarkably lower than those in the COPD stabilization group, again with statistically significant differences being observed (P< 0.05 and P< 0.01, respectively). The percentage of FEV1 in the predicted value and the FEV1/FVC level in patients in the COPD aggravation group were significantly lower than those of patients in the COPD stabilization group, and the differences were statistically significant (P< 0.05). Serum sTREM-1 was negatively correlated with FEV1/FVC, the percentage of FEV1 in the predicted value, and APT (r = -0.425, -0.486, -0.426; P< 0.05 or P< 0.01), and positively correlated with CRP, PCT, CTRP5 and sST2 (r = 0.516, 0.481, 0.489, 0.517, P< 0.01). Serum CTRP5 was found to be negatively correlated with FEV1/FVC, the percentage of FEV1 in the predicted value, and APT (r = -0.513, -0.506, -0.478, P< 0.05 or P< 0.01), and positively correlated with CRP, PCT and sST2 (r = 0.481, 0.416, 0.526, P< 0.05 or P< 0.01). Serum sST2 was negatively correlated with FEV1/FVC, the percentage of FEV1 in the predicted value, and APT (r = -0.461, -0.518, -0.514, P< 0.01) and was positively correlated with CRP and PCT (r = 0.561, 0.437, P< 0.05 or P< 0.01). Conclusion: The serum sTREM-1, CTRP5 and sST2 levels in COPD patients were highly expressed and increased with the severity of the disease. Each of them showed a significantly positive correlation, which may be related to the severity of the disease.