Chronic Obstructive Pulmonary Disease (COPD) is characterized by chronic bronchitis associated with emphysema that generates elastin-derived peptides (EP) impacting many immune populations. Innate Lymphoid Cells (ILC) play a role in many pathologies including COPD. However, the mechanisms regulating their functionalities, especially linked to EP, are not yet known. Our goal is to understand the mechanisms of ILC regulation and orientation induced by EP in COPD. ILC isolated from the blood of COPD patients and controls were used for studies including phenotypic characterization by flow cytometry and in vitro functional experiments in different conditions to examine the impact of EP. Publicly available single-cell RNA sequencing data comparing COPD patients and controls were used to analyze ILC regulation by EP. Our results demonstrated that the proportion of ILC2 was increased and the proportion of ILC3 was decreased in the blood of COPD patients. In addition, we observed a significant increase in the expression of cytokines associated with the different types of ILC in COPD patients indicating an increase in activation. Moreover, ILC cultured with serum from COPD patients with emphysema or with supernatants of EP-stimulated macrophages showed an increase in the proportion of ILC2. Further analyses showed an increase of the cytokines IL-4, -5 and -13 in the serum of COPD patients and the supernatant of EP-stimulated macrophages. Altogether, our results indicate an orientation of ILC towards an ILC2 profile in COPD patients as well as a general activation of ILC represented by an increase in their cytokine secretion capacity. Moreover, in vitro culture experiments suggest a role of EP, via their impact on macrophage, in the regulation of ILC during COPD.