It is not uncommon for laboratory animals to be fasted prior to experimentation. Fasting evokes marked reductions in heart rate (HR), blood pressure (BP), heat production and oxygen consumption (VO(2)) in rodents. Mice with diet-induced obesity exhibit elevated HR and BP, and lower VO(2) and heat production in the fed condition versus their lean counterparts. It is unknown whether body composition alters the tempo of response to fasting. We tested the hypothesis that cardiovascular and metabolic responses to fasting are delayed in obese versus lean male C57BL/6J mice. In the fed condition, mice that consumed high-fat (HF, 45% fat) chow for 98 ± 5 days had elevated (P < 0.05) body fat percentage (DEXA), serum leptin (ELISA), HR and BP (72-h biotelemetry), and lower (P < 0.05) heat production and VO(2) (72-h metabolic chamber) versus animals that consumed standard chow (CON, 10% fat; n = 16 per group). HR, BP, VO(2), heat production and serum leptin decreased (all P < 0.05) in response to a 16-h fast (16:00-08:00 h) in both groups. Although the overall fold changes in cardiovascular and metabolic parameters were similar in magnitude among animals, fasting-induced reductions in cardiovascular and metabolic variables occurred ∼4 and ∼7 h earlier (P < 0.05), respectively, in HF versus CON mice. These findings indicate that while metabolic and cardiovascular stress evoked by a 16-h fast at 22°C is not different between HF and CON mice, fasting-induced responses occur sooner in obese animals.