Objective <p>Galectin-7, a β-galactoside-binding lectin involved in inflammation, immune regulation, and apoptosis, has been implicated in the development and progression of various lung diseases. Inflammation, immune dysregulation, and epithelial cell apoptosis are key pathophysiological mechanisms underlying chronic obstructive pulmonary disease (COPD). However, the clinical significance of galectin-7 in COPD remains unclear. This study aimed to investigate the association between sputum galectin-7 levels and the clinical characteristics and prognosis of patients with COPD.</p> Methods <p>In this prospective study, 150 patients with stable COPD and 50 healthy controls were enrolled. Demographic data, clinical parameters, and sputum samples were collected. Baseline galectin-7 concentrations in sputum supernatants were measured using an enzyme-linked immunosorbent assay (ELISA). Patients with COPD were followed for one year to document acute exacerbation events. Among COPD patients, Spearman correlation analysis and multivariable linear regression were performed to examine the associations between galectin-7 levels and clinical parameters or inflammatory markers, adjusting for sex, age, smoking status, and body mass index (BMI). Multivariable Poisson regression and logistic regression models were further applied to assess the relationship between galectin-7 levels and acute exacerbations within one year, with adjustment for the number of exacerbations in the previous year, sex, age, smoking status, BMI, and post-bronchodilator FEV1% predicted (Post-BD FEV1% pred).</p> Results <p>After adjustment in the analysis of covariance, galectin-7 levels were significantly lower in patients with GOLD III–IV than in healthy controls and patients with GOLD I–II (P &lt; 0.05). Multivariable linear regression analyses indicated that galectin-7 levels were significantly associated with multiple clinical indicators and inflammatory markers. In the multivariable Poisson regression model, each 10 ng/mL increase in sputum galectin-7 was associated with a 15.7% reduction in the risk of acute exacerbations within one year (RR, 0.843; 95% CI, 0.716–0.973; P = 0.028). In the multivariable logistic regression model, each 10 ng/mL increase in sputum galectin-7 was associated with a 35.1% lower risk of frequent acute exacerbations within one year (OR, 0.649; 95% CI, 0.424–0.923; P = 0.029).</p> Conclusion <p>Lower sputum galectin-7 levels are associated with later stages and an increased risk of future acute exacerbations in COPD, suggesting that galectin-7 may be a promising biomarker related to disease severity and prognosis.</p> Trial Registration <p>This study was registered in the International Clinical Trials Registry (NCT03240315). Trial registration on July 31, 2017.</p>