Mechanical ventilation of patients with severe asthma is associated with elevated airway pressures that may contribute to increased physiologic dead space. To our knowledge, no previous reports have considered the effect of intravascular volume status on dead space fraction. We herein describe three patients whose dead space decreased by a mean of 4.2% in response to intravascular volume expansion with 250 or 500 mL of normal saline solution administered as part of their routine treatment. No significant changes in CO2 production, minute volume, or airway pressures occurred over the time interval. We conclude with a brief discussion of potential mechanisms to explain these findings and their potential clinical application.