The goal of this study was to test whether the "loss of the complexity" hypothesis can be applied to compare the metabolic patterns of mouse models with known differences in metabolic and endocrine function as well as life span. Here, we compare the complexity of locomotor activity and metabolic patterns (energy expenditure, VO₂, and respiratory quotient) of the long-lived growth hormone receptor gene deleted mice (GHR ^-/-) and their wild-type littermates. Using approximate entropy as a measure of complexity, we observed greater metabolic complexity, as indicated by greater irregularity in the physiological fluctuations of the GHR^-/- mice. Further analysis of the data also revealed lower energy costs of locomotor activity and a stronger relationship between locomotor activity and respiratory quotient in the GHR^-/- mice relative to controls. These findings suggest underlying differences in metabolic modulation in the GHR ^-/- mice revealed especially through measures of complexity of their time-dependent fluctuations.