Cardiac injury or stress increases circulating catecholamines (CA), stimulating cardiac β adrenergic receptors (βAR) and adaptive positive inotropy. Under such conditions of increased energy demand, cardiomyocyte metabolism and bioenergetics are altered to maintain cellular function and survival. During chronic CA stimulation, however, receptor desensitization occurs, contributing to loss of contractile reserve and heart failure (HF) development. This progression to HF is again marked by metabolic and bioenergetic changes that remain incompletely understood. Notably, chronic CA exposure induces insulin resistance (IR) in the heart, which decreases substrate uptake and prevents protective signaling. Our laboratory has shown that G protein-coupled receptor kinase 2 induces IR in the heart following myocardial infarction. However, neither the molecular mechanisms of CA-induced IR, nor its effects on cardiomyocyte bioenergetics are well characterized. We hypothesize that βAR stimulation induces IR by decreasing insulin-stimulated mitochondrial respiratory capacity, thus, compromising cardiomyocyte survival during stress. Bioenergetics were evaluated by measuring cellular respiration under coupled (basal) and uncoupled (maximal) conditions. Our results show that acute insulin treatment selectively increases (25%) maximal and reserve respiratory capacity in the presence of glucose, which positively correlates with cellular survival. This effect is completely inhibited with chronic βAR stimulation using isoproterenol or clenbuterol, as is glucose transporter (GLUT4) translocation to the membrane. A similar effect is reproduced by high glucose and/or palmitate-induced IR. Notably, chronic βAR stimulation does not affect basal or maximal respiration, while acute stimulation increases basal respiration (25%). In short, the data demonstrate a unique insulin-induced increase in mitochondrial respiratory capacity in cardiomyocytes that is antagonized by chronic CA stimulation. We propose that this effect contributes to the detrimental effects of βAR stimulation during HF. Thus, understanding this phenomenon and its mechanisms is critical for inhibiting IR and improving cardiac metabolism and function during HF.