Due to its extremely finite energy reservoir, the brain is heavily reliant on blood-borne metabolites and their delivery through the blood-brain barrier to meet its regional and transient bursts of energetic needs. Despite this reliance, few studies investigating the controversial question of neuronal lactate use measure the contribution of peripheral metabolites. In this study, we investigated the impact of peripheral transporter inhibition on cortical extracellular metabolite fluctuations. The glucose (GLUT1; WZB117) and monocarboxylate (MCT1; AZD3965) transporter inhibitor, were administered intraperitoneally to adult male mice. Subsequently, cortical extracellular glucose and lactate in the primary motor cortex were monitored in awake mice with the use of biosensors. Extracellular metabolite fluctuations were assessed following motor behaviors and metabolic challenges (intraperitoneally administered glucose, lactate or fructose). Dual inhibition of both GLUT1 and MCT1 resulted in an immediate increase in endothelial MCT1 protein expression, elevated blood lactate and extracellular brain glucose. MCT1 inhibition reduced extracellular lactate during motor behaviors, implicating peripheral lactate and blood-brain barrier transporter in activity-induced increases in cortical lactate. Finally, western-blot measures revealed that endothelial MCT1 and GLUT1 expression can be altered within minutes of inhibition. These findings suggest an important contribution of endothelial MCT1 and blood lactate to extracellular glucose pools and possible glucose-sparing mechanisms as well as hint to preferential upregulation of monocarboxylate use and transport during times of reduced transport capacity or metabolite availability. Overall, this work highlights the highly adaptable nature of the blood-brain barrier metabolite transport systems.