ABSTRACT: Pre-diabetes (Pre-D) is characterized by elevated glycated hemoglobin and plasma glucose and is a clinical precursor to type 2 diabetes mellitus (T2D). Pre-D currently affects ~90 million Americans. Both Pre-D and T2D are highly associated with cardiovascular disease and among the top five causes of mortality worldwide. Exercise is the cornerstone of management and is most efficacious during the Pre-D stage when glycemia is below the diabetic threshold. However, excessive fatigability during exercise (i.e., exercise induced reductions in force or power of the limb muscles) limits exercise performance in people with Pre-D. Our laboratory demonstrated that (1) across the diabetic spectrum, people with Pre-D and T2D have greater fatigability of limb muscles than controls due to mechanisms within the muscle, and (2) fatigability in people with T2D was associated with a reduced blood flow to the exercising muscle. It is unknown, however, if people with Pre-D have impaired vascular function and oxygen delivery that leads to an increased fatigability. Our central hypothesis is that impaired vascular function impedes blood flow and blunts subsequent oxygen delivery to skeletal muscle during exercise, resulting in excessive fatigability of limb muscles in people with Pre-D.