Objective To investigate Serum lipoprotein associated phospholipase A2 (Lp-PLA2) and endostatin (ES) levels in patients with chronic obstructive pulmonary disease (COPD) and their diagnostic value for those complicated with pulmonary hypertension (PAH). Methods A total of 112 COPD patients admitted to our hospital from June 2020 to November 2021 were selected. They were reclassified into patients with complicated PAH (n=51) and patients without complicated PAH (n=61) according to whether they had complicated PAH. Meanwhile, 60 healthy people of the same age group were selected for hospital examination (control group). The serum Lp-PLA2 and ES levels in different groups were compared. The correlation between serum Lp-PLA2 and ES levels and FEV1 and FEV1/FVC was analyzed by Pearson analysis. Risk factors of COPD complicated with PAH were analyzed by binary logistics analysis. ROC curve was used to evaluate the diagnostic value of serum Lp-PLA2 and ES levels in COPD patients complicated with PAH. Results The serum levels of Lp-PLA2 and ES in COPD patients complicated with PAH were higher than those in COPD patients without PAH (all P＜0.05). Serum Lp-PLA2 and ES levels were negatively correlated with FEV1% and FEV1/FVC in COPD patients (all P＜0.05). Binary Logistic regression analysis showed that higher levels of FEV1% and FEV1/FVC were protective factors for COPD complicated with PAH, while higher levels of Lp-PLA2 and ES were risk factors for COPD complicated with PAH (all P＜0.05). ROC curve showed that the AUC value of Lp-PLA2 combined with ES was significantly higher than that of single Lp-PLA2 or ES, and its sensitivity and specificity were 80.39 and 83.61, respectively. Conclusion The serum levels of Lp-PLA2 and ES in COPD patients are increased, and are closely related to lung function. The combined detection of Lp-PLA2 and ES has good diagnostic efficacy for COPD patients complicated with PAH, and provides powerful help for early clinical targeted treatment