Chronic obstructive pulmonary disease (COPD) is the most frequently encountered progressive lung disease in clinical practice. This study sought to determine the predictive ability of the tumor biomarker cancer antigen-125 (CA-125) in the identification of COPD in a cohort of 284 patients with COPD living at high altitude (with an average elevation of over 2500 m).Patients were classified by pleural effusion volumes into 4 categories and serum CA-125 concentrations were measured in each category. The analyses revealed that CA-125 concentrations were positively and significantly correlated with pleural effusion volume. CA-125 concentrations were also positively correlated with pulmonary heart disease and acute exacerbations of COPD, and negatively correlated with pulmonary hypertension.The study evidence suggests that serum CA-125 concentrations are positively correlated with the risk of pleural effusions among patients with COPD living in high-altitude areas, and that CA-125 concentrations are also correlated with pulmonary heart disease, acute exacerbations, and pulmonary hypertension.