This study examined the sedative effect of, and hemodynamic response to dexmedetomidine administration in propofol-sedated swine. Sixteen swine were subjects. After anesthetic induction and preparation, the propofol infusion rate was adjusted to maintain a bispectral index (BIS) value between 55 and 65 (i.e., baseline). With the propofol infusion rate fixed at the baseline rate, dexmedetomidine was infused continuously at a rate of 0.2, 0.4, and 0.7 μg·kg ^–1·h^–1 for one hour at each rate. The BIS value and hemodynamic parameters were recorded at each step. Dexmedetomidine decreased the BIS value, mean arterial blood pressure, heart rate, cardiac output, and mixed venous oxygen saturation in a dose-dependent manner. The systemic vascular resistance (SVR) did not change, but the pulmonary vascular resistance (PVR) increased. Oxygen delivery (DO₂) and oxygen consumption (VO₂) decreased. A small dose of dexmedetomidine (0.2 μg·kg^–1·h^–1) greatly enhanced the sedative effects of propofol with only small changes in hemodynamics and systemic oxygen balance, suggesting it may be useful in reducing the propofol dose requirement. However, dexmedetomidine 0.4 μg·kg^–1·h ^–1 suppressed cardiac contractility, and 0.7 μg·kg^–1·h^–1 induced hemodynamic instability and further systemic oxygen imbalance while the additional sedative effect was limited. A lower dose of dexmedetomidine may be recommended when using it in combination with propofol.