A better understanding of the mechanisms governing virus-induced exacerbations of chronic obstructive pulmonary disease (COPD) is urgently needed to develop more effective therapeutic approaches. Animal models are invaluable tools for gaining mechanistic insight into innate immunity. Here, we describe the methods required to establish a short-term mouse model comprising elastase administration to induce features of COPD, combined with infection using the minor group rhinovirus serotype A1 (RV-A1). This model recapitulates the hallmark features of human virus-induced COPD exacerbation and facilitates the study of mechanisms that drive these episodes.