Abstract: OBJECTIVE Patients with chronic obstructive pulmonary disease (COPD) complicated with lower respiratory infection (LRI) may experience severe respiratory symptoms, leading to increased medical costs and potential patient deaths. This study aims to analyze the health economic burden following LRI and provide directions for reducing patients' medical expenses. METHODS A cross-sectional survey was conducted to collect the cost details and antibacterial drug usage information of 2 989 inpatients diagnosed with COPD at the Second People's Hospital of Gansu Province from 2022 to 2024. These patients were divided into an infection group (1,545 cases) and a non-infection group (1,444 cases) based on whether they developed LRI. Differences in medical costs and length of hospital stay between the two groups were compared. RESULTS Among 2 989 inpatients with COPD, the usage rate of antibacterial drugs was 78.72%, showing a decreasing trend year by year. Among the 2 353 patients who used antibacterial drugs, 12.79% of patients received ≥three types of antibacterial drugs, also showing a decreasing trend year by year (χ²=33.022, P<0.001). 51.34% of patients received antibacterial drugs for ≥10 days, showing an increasing trend year by year (χ²=8.406, P=0.015). Patients in the LRI infection group had higher hospitalization costs and longer hospital stays than those in the non-infection group, excluding surgical costs. Patients infected with multidrug-resistant bacteria had higher medical costs and longer hospital stays than those infected with ordinary LRI. Further comparison of total hospitalization costs among patients with different characteristics of LRI infections showed that patients in the infection group who were male, had a hospital stay of ≥20 days, had comorbidities such as heart disease, received antibacterial drugs for ≥10 days, received ≥three types of antibacterial drugs, and had a history of invasive procedures, tended to have higher total hospitalization costs (P<0.05). CONCLUSIONS LRI infection imposes a significant health economic burden on patients. In the future, efforts to prevent and control infections caused by multidrug-resistant bacteria need to be intensified to reduce medical costs.