Purpose: The objective of this study was to assess the effectiveness of graduated compression socks (GCS) on enhancing muscle blood flow and oxygenation during exercise and recovery in healthy subjects. Methods: Twelve healthy volunteers completed a protocol involving baseline, exercise, and recovery periods with and without GCS. Each test was repeated twice to assess repeatability of the results. The applied sock pressure was measured prior to experimentation using a custom pressure sensing system, and modified as necessary using tensor bandages to control the applied load. During each of the experimental phases, blood velocity in the popliteal artery, calf muscle tissue oxygenation, muscle activity, heart rate, blood pressure, cardiac output, and applied pressure from the sock were measured. Popliteal artery diameter was measured during baseline and recovery periods. Results: The GCS significantly reduced deoxyhemoglobin (HHb) in the leg during baseline (HHb, p = 0.001) and total blood volume and HHb in the leg during exercise (total hemoglobin, p = 0.01; HHb, p = 0.02). However, there were no differences in leg muscle blood flow velocity or any other variables with and without GCS at baseline, exercise, or recovery. Interestingly, it was found that the local applied sock pressure was very sensitive to the sock application process and, furthermore, the pressure varied considerably during exercise. Conclusions: No significant changes were observed in measures reflecting oxygen delivery for healthy subjects using GCS during exercise and recovery. Applied sock pressure was carefully controlled, thus eliminating the sock application process as a variable.