Spontaneous daily torpor as well as cold- and fasting-induced torpor is observed in many mammals and birds. The frequency and intensity of torpor are largely influenced by well characterized environmental conditions. The inherited component of phenotypic variation in body temperature regulation is, however, only poorly understood. The identification of mutations affecting physiological body temperature regulation may elucidate novel molecular mechanisms contributing to metabo- and thermoregulatory behavior. Therefore, we monitored rectal body temperature (Tb) in six inbred mouse strains (129/SvJ, AKR/J, C57BL/6J, C57BL/6N, Balb/cJ, and SWR/J) and in 146 mutant mouse lines and age-matched controls. Measurements were taken under ad libitum conditions and in response to either food restriction or food deprivation. Inbred mice showed considerable strain-specific differences in Tb under ad libitum feeding as well as after food restriction and deprivation. Tb was on average ≈0.4°C higher in females as compared to males in all inbred lines. The thermoregulatory response to food restriction reflected a trade-off between changes in Tb and body mass with the least body mass loss in mice exhibiting the largest drop in Tb. In mutant mouse lines under ad libitum feeding Tb of 36 out of 146 was significantly higher (15 lines) or lower (21 lines) as compared with controls. In response to food restriction and deprivation, 13 mutant mouse lines with augmented Tb reduction were found two of which showed rectal Tb lower than 31°C. In conclusion, Tb under ad libitum as well as in response to food deprivation is an important indicator for genotype-related differences on systemic functions. Depending on the test conditions 25–32% of all mutant lines showed significant alterations in Tb.