Whole-body vibration (WBV) is currently used to enhance performance and treat injuries even though we lack an understanding of how WBV influences physiological processes. An improved understanding of the physiological effects of WBV could lead to protocols to speed healing or treat pathologies. This study examined the acute effects of WBV on peripheral blood perfusion, muscle oxygenation, motoneuron pool excitability, and sensory nerve conduction velocity. Fourteen healthy participants [9 women (21.7 ± 2.4 years); 5 men (20.8 ± 1.1 years)] completed a 5 min bout of WBV (50 Hz, 2 mm amplitude). Measures were assessed pre-treatment and at 0, 5, 10, 15, and 20 min post-treatment. WBV significantly increased superficial skin temperature (P < 0.0005) and total hemoglobin (P = 0.009), had no effect of oxyhemoglobin (P = 0.186), increased deoxyhemoglobin (P < 0.0005), inhibited the soleus Hoffmann reflex (P = 0.007), and had no effect on sural sensory nerve conduction velocity (P = 0.695). These results suggest that an acute bout of WBV influences physiological processes in both the circulatory and the nervous systems.