Objective To explore the expression levels and clinical significance of serum long noncoding RNA myocardial infarction associated transcript (lncRNA MIAT) and microRNA-515-5p (miR-515-5p) in elderly patients with chronic obstructive pulmonary disease (COPD) at different periods. Methods From April 2021 to June 2023, 90 elderly patients with acute exacerbation of COPD treated in Huaibei People’s Hospital were selected as a COPD acute exacerbation group, 88 elderly patients with stable COPD as a COPD stable group, and 90 healthy elderly individuals undergoing physical examination as a control group. The white blood cell count (WBC) and serum lncRNA MIAT and miR-515-5p expression levels were detected in all subjects, blood gas analysis and pulmonary function indexes [oxygenation index (PaO2/FiO2), arterial blood carbon dioxide partial pressure (PaCO2), ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC), and FEV1 as a percentage of predicted value (FEV1%pred)] were detected in the patients with COPD. The correlation between serum lncRNA MIAT, miR-515-5p and smoking, WBC, blood gas analysis and pulmonary function indexes were analyzed in the elderly patients with acute exacerbation of COPD. The influencing factors of acute exacerbation of COPD, and the value of serum lncRNA MIAT, miR-515-5p in predicting the occurrence of acute exacerbation of COPD were also analyzed. Results The smoking proportion, WBC, serum lncRNA MIAT expression levels of the control group, the COPD stable group and the COPD acute exacerbation group were increased in turn, serum miR-515-5p expression levels were decreased in turn (P<0.05). Compared with the COPD stable group, PaCO2 was significantly increased in the COPD acute exacerbation group, while PaO2/FiO2, FEV1/FVC and FEV1%pred were significantly decreased (P<0.05); serum lncRNA MIAT in the elderly patients with acute exacerbation of COPD was positively correlated with smoking, WBC, PaCO2 (P<0.05), and negatively correlated with PaO2/FiO2, FEV1/FVC, FEV1%pred, miR-515-5p (P<0.05); serum miR-515-5p was negatively correlated with smoking, WBC, PaCO2 (P<0.05), and positively correlated with PaO2/FiO2, FEV1/FVC, FEV1%pred (P<0.05). Smoking, WBC, PaCO2, and lncRNA MIAT were risk factors affecting the acute exacerbation of COPD patients, PaO2/FiO2, FEV1/FVC, FEV1%pred, miR-515-5p were protective factors affecting the acute exacerbation of elderly COPD patients (P<0.05). The area under the ROC curve (AUC) of serum lncRNA MIAT, miR-515-5p and their combination in predicting acute exacerbation in elderly COPD patients were 0.823, 0.862 and 0.919, respectively, higher than the AUC predicted by serum lncRNA MIAT and miR-515-5p separately (P<0.05). Conclusions Serum lncRNA MIAT expression was high in elderly patients with COPD, and serum miR-515-5p expression was low, and the changes of both were more obvious in patients with acute exacerbation. Both were correlated with blood gas analysis and pulmonary function indexes in patients with acute exacerbation, and have high value in predicting the occurrence of acute exacerbation in elderly patients with COPD.