Abstract The purpose of the review is to highlight the influences of ambient temperature ( T a) and caloric restriction (CR) on metabolism, cardiovascular function and behavior in mice. Standard vivarium ambient temperatures ( T a≅23 °C) are a mild cold stress for mice requiring elevated metabolic rate and food intake. Increasing T a into the zone of thermoneutrality (TMN≅29–33 °C) markedly reduces food intake, metabolic rate, heart rate (HR) and blood pressure in mice. Mice are members of a diverse, yet unique group of homeothermic animals that respond to thermal and energetic challenges by allowing body temperature ( T b) to fall to less than 31 °C, a condition known as torpor. In mice housed at standard T a, torpor is induced by a single night of fasting or a few days of CR. The mechanisms responsible for initiating torpor are related to reduced caloric availability, but do not require leptin. Mice housed at TMN and subjected to CR exhibit physiologic reductions in metabolic rate and HR, but do not appear to enter torpor. Finally, mice exhibit differential locomotor activity responses during CR that depends on T a. At standard T a, mice display increased light-phase home-cage activity with CR. This response is virtually eliminated when CR is performed at TMN. We suggest that researchers using mice to investigate energy homeostasis and cardiovascular physiology carefully consider the influence of T a on physiology and behavior.