We measured the standard metabolic rate of paedomorphic Mole Salamanders (Ambystoma talpoideum) from South Carolina. Despite an absence of body size differences between females and males, analysis of covariance demonstrated metabolic rates (mL O2/h) were significantly influenced by an interaction between sex and body size. The interaction appeared as a result of changes in the size-metabolism relationship in males (a steeper slope in the size-metabolism regression in small males as compared to large males), whereas the relationship remained constant in females, regardless of size. We hypothesize that the observed differences are attributable to differences in reproductive physiology between the sexes. The results of this study underscore the need to evaluate the potential interactions among relevant variables in studies of metabolism, which heretofore have been disregarded in studies of salamander physiology.