AMPK has an established role in preventing myocardial ischemic injury and heart failure. Recent research indicates that the LKB1-AMPK pathway is also critical in atrial biology and disease. Loss of LKB1 or AMPK leads to atrial structural remodeling and the development of spontaneous atrial fibrillation in mice. The role of AMPK in atrial metabolic homeostasis is not well understood. Using a genetic model of selective atrial AMPK deletion, we have found that AMPK is essential for maintaining normal mitochondrial ultrastructure, and regulates critical proteins responsible for substrate metabolism, electron transport and TCA cycle function in the atria. AMPK deficiency also leads to a shift in substrate preference away from fatty acid towards increased carbohydrate utilization for oxidative metabolism. Oxidative stress occurs and may contribute to the atrial electrical remodeling that is characteristic of atrial AMPK deficiency. Thus, AMPK has an important role in the atria and further research is needed to determine whether loss of AMPK activity might contribute to the pathogenesis of atrial remodeling and the development of atrial fibrillation in human disease.