The purpose of this study was to investigate the potential mechanisms behind the blood flow restriction (BFR) stimulus in the absence of exercise. Nine participants completed a 10 minute time control and then a BFR protocol. The protocol was five, 5-minute bouts of inflation with 3-minutes of deflation between each bout. The pressure was set relative to each individual's thigh circumference. Significant increases in muscle thickness were observed for both the vastus lateralis (VL) [6%, p = 0.027] and rectus femoris (RF) [22%, p = 0.001] along with a significant decrease in plasma volume [15%, p = 0.001]. Ratings of discomfort during the BFR protocol peaked at 2.7 (light discomfort). There were no significant changes with whole blood lactate, electromyography (EMG), or heart rate (HR), however, there was a trend for a significant increase in HR during the 5th inflation (p = 0.057). In conclusion, this is the first study to demonstrate that the attenuation of both muscle atrophy and declines in strength previously observed with brief applications of BFR may have been mediated through an acute fluid shift induced increase in muscle size. This is supported by our finding that the changes in muscle thickness are maintained even after the cuffs have been removed.