Importance: Little is known about the natural course of oxygen desaturation in acute bronchiolitis. Information on risk factors associated with desaturation as well as the time to desaturation in infants with bronchiolitis could help physicians better treat these infants before deciding whether to hospitalize them. Findings: In this cohort study of 239 infants, desaturation occurred in most infants, regardless of whether they were hospitalized or discharged home. A more severe initial clinical presentation was the only risk factor associated with desaturation, but desaturation was not a risk factor associated with rehospitalization. Meaning: These findings suggest that desaturation in acute bronchiolitis was frequent, especially for infants with a more severe clinical presentation, but it was not a risk factor associated with rehospitalization.