The relationship between heart beat frequency and the rate of oxygen consumption for different species of birds and mammals is influenced by body size, the type of exercise being undertaken and its intensity. Here a model is presented combining allometric scaling and exercise-induced variations in oxygen consumption and blood flow, when birds and mammals undergo their primary mode of locomotion. Novel relationships, common to the regulatory systems of all endotherms, are found to relate the rate of oxygen consumption, heart-rate, body and heart mass in 24 species of endotherms spanning 5 orders of body mass. We show that these relationships can be derived from linearity between heart-rate and the arteriovenous oxygen difference, present in data from exercise-attuned humans. We find that the metabolic rate of endotherms undergoing their primary mode of locomotion across a range of exercise intensities is quadratically related to heart-rate and that body mass is inferior to heart mass as a predictive scaling variable. The model facilitates graphical comparisons between species, and enables metabolic costs to be extrapolated from heart-rate data whenever direct measurements of oxygen consumption prove prohibitively challenging.