To determine the cardiopulmonary changes associated with intravenous (IV) infusions of dexmedetomidine at equipotent isoflurane-dexmedetomidine concentrations compared with isoflurane alone. Prospective, randomized, crossover experiment. Six adult intact female mixed-breed dogs weighing (mean ± SD [range]) 23.3 ± 3.8 (17.8–29.4) kg. Anesthesia was induced and maintained with isoflurane in oxygen. Measurements of respiratory rate (fR), heart rate (HR), systemic and pulmonary arterial pressures (SAP, DAP, MAP, MPAP), central venous pressure (CVP), pulmonary arterial occlusion pressure (PAOP), cardiac index (CI), left and right ventricular stroke work index (LVSWI, RVSWI), systemic and pulmonary vascular resistance index (SVRI, PVRI), arteriovenous shunt ( Q ˙ s / Q ˙ t ), oxygen delivery ( D ˙ O 2 ), oxygen extraction ratio (O2ER), oxygen consumption, arterial and mixed venous blood gases, and arterial packed cell volume (PCV) were obtained 30 minutes after instrumentation at an end-tidal isoflurane concentration (Fe’Iso) of 1.73 ± 0.02% (1.3 MAC). Dexmedetomidine was administered IV at 0.5 or 3 μg kg−1 over 6 minutes followed by an infusion at 0.5 (LD) or 3 μg kg−1 hour−1 (HD), respectively, with Fe’Iso at 1.41 ± 0.02 (LD) or 0.72 ± 0.09% (HD). Measurements were taken at 10, 30, 60, 90, 120, 150 and 180 minutes after the start of the infusion. The low dose produced significant decreases in HR, increases in SAP, DAP, CVP, MPAP, PAOP and LVSWI, but no change in CI. HD produced significant increases in SAP, MAP, DAP, CVP, PAOP, SVRI, LVSWI, O2ER and PCV and significant decreases in CI and D ˙ O 2 . There were significant differences between treatments in HR, MAP, DAP, CVP, MPAP, PAOP, CI, SVRI, HCO 3 - , SBE, D ˙ O 2 , O2ER and Q ˙ s / Q ˙ t . Cardiopulmonary changes associated with LD were within clinically accepted normal ranges whereas HD produced clinically significant changes. The LD may be useful as an anesthetic adjunct in healthy dogs.