Chronic obstructive pulmonary disease (COPD), a chronic and progressive disease characterized by persistent respiratory symptoms and progressive airflow obstruction, has attracted extensive attention due to its high morbidity and mortality. Although the understanding of the pathogenesis of COPD has gradually increased because of increasing evidence, many questions regarding the mechanisms involved in COPD progression and its deleterious effects remain unanswered. Recent advances have shown the potential functions of endoplasmic reticulum (ER) stress in causing airway inflammation, emphasizing the vital role of unfolded protein response (UPR) pathways in the development of COPD.A comprehensive search of major databases including PubMed, Scopus, and Web of Science was conducted to retrieve original research articles and reviews related to ER stress, UPR, and COPD.The common causes of COPD, namely cigarette smoke (CS) and air pollutants, induce ER stress through the generation of reactive oxygen species (ROS). UPR promotes mucus secretion and further plays a dual role in the cell apoptosis-autophagy axis in the development of COPD. Existing drug research has indicated the potential of UPR as a therapeutic target for COPD.ER stress and UPR activation play significant roles in the etiology, pathogenesis, and treatment of COPD and discuss whether related genes can be used as biomarkers and therapeutic targets.© 2023. Springer Nature Switzerland AG.