OBJECTIVE To evaluate the safety and efficacy of oxygen administration by use of a high-flow nasal cannula (HFNC) in sedated clinically normal dogs. ANIMALS 6 healthy adult dogs undergoing routine dental prophylaxis. PROCEDURES Dogs were sedated with butorphanol tartrate and dexmedetomidine. An esophageal balloon catheter was inserted into the esophagus, a double-pronged nasal cannula was inserted into the nares, and a catheter was inserted into the dorsal pedal artery. Dogs were positioned in right lateral recumbency. After a 6-minute acclimation period, baseline blood gas values and transpulmonary pressure were measured. Dogs then received supplemental oxygen via conventional oxygen therapy (COT) at a rate of 100 mL/kg/min (COT-100 treatment) and an HFNC at a rate of 20 L/min (HF-20 treatment) and 30 L/min (HF-30 treatment). Arterial blood gas and transpulmonary pressure were measured after a 6-minute acclimation period for each oxygen delivery method. Radiographs were obtained before and after oxygen administration to evaluate gastric distension. RESULTS Median Pao2 was significantly higher for HF-20 (519.9 mm Hg) and HF-30 (538.1 mm Hg) treatments, compared with median Pao2 for the COT-100 treatment (202.9 mm Hg). The Pao2 did not differ significantly between the HF-20 and HF-30 treatments. There was no significant difference in Paco2 or change in transpulmonary pressure between baseline and any oxygen delivery method. CONCLUSIONS AND CLINICAL RELEVANCE In this study, HFNC appeared to be a safe and effective method for oxygen delivery to sedated healthy dogs. Further studies are needed to evaluate use of HFNCs for oxygen administration to hypoxemic patients.