Abstract Objective A suite of adaptations facilitating endurance running (ER) evolved within the hominin lineage. This may have improved our ability to reach scavenging sites before competitors, or to hunt prey over long distances. Running economy (RE) is a key determinant of endurance running performance, and depends largely on the magnitude of force required to support body mass. However, numerous environmental factors influence body mass, thereby significantly affecting RE. This study tested the hypothesis that alternative metabolic strategies may have emerged to enable ER in individuals with larger body mass and poor RE. Methods A cohort of male (n = 25) and female (n = 19) ultra-endurance runners completed submaximal and exhaustive treadmill protocols to determine RE, and V̇O_2Max. Results Body mass was positively associated with sub-maximal oxygen consumption at both LT1 (male r=0.66, p<0.001; female LT1 r=0.23, p=0.177) and LT2 (male r=0.59, p=0.001; female r=0.23, p=0.183) and also with V̇O_2Max (male r=0.60, p=0.001; female r=0.41, p=0.046). Additionally, sub-maximal oxygen consumption varied positively with V̇O_2Max in both male (LT1 r=0.54, p=0.003; LT2 r=0.77, p<0.001) and female athletes (LT1 r=0.88, p<0.001; LT2 r=0.92, p<0.001). Conclusions The results suggest that, while individuals with low mass and good RE can glide economically as they run, larger individuals can compensate for the negative effects their mass has on RE by increasing their capacity to consume oxygen. The elevated energy expenditure of this low-economy high-energy turnover approach to ER may bring costs associated with energy diversion away from other physiological processes, however.