A myocardial infarction (MI) is the death of cardiomyocytes due to deprivation of blood flow to cardiac muscle. Although the respiratory system is a significant contributor to one-month mortality, there is a poor understanding of the acute changes following MI. The aim of this study was to address the early pathogenesis of the respiratory system by investigating the acute dysfunction of the lungs/ diaphragm post-MI. MIs were surgically induced in CD-1 male mice by permanent ligation of the left anterior descending coronary artery. Pulmonary dysfunction, characterized by edema, inflammation, and hemoglobin desaturation, was transient and peaked at 7 days post-MI. Diaphragm dysfunction, defined by reduced maximal in vivo strength, had a delayed onset but was persistent to study endpoint. A deeper understanding of the pathophysiological sequelae may direct future research into therapeutically targeting the respiratory system as a primary source of injury, changing the way that patients are treated post-MI.