OBJECTIVE: To determine the effect of intranasal oxygen administration on blood gas variables and outcome in neonatal calves with respiratory distress syndrome (RDS). DESIGN: Retrospective case series. ANIMALS: 20 neonatal calves with RDS. PROCEDURES: Arterial partial pressure of oxygen (PaO(2)), arterial partial pressure of carbon dioxide, and arterial oxygen saturation (SaO(2)) before and after intranasal administration of oxygen were analyzed. RESULTS: There were significant increases in PaO(2) and SaO(2) in the first 24 hours after oxygen administration was begun, with mean +/- SD PaO(2) increasing from 38.4+/-8.8 mm Hg to 58.7+/-17.8 mm Hg during the first 3 hours of treatment. Calves with PaO(2)>55 mm Hg within the first 12 hours after oxygen administration was begun had a significantly higher survival rate (9/10) than did calves that did not reach this threshold (4/10). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that intranasal oxygen administration was a simple method of improving blood gas variables in neonatal calves with RDS and that PaO(2) could be used to predict outcome.