OBJECTIVE To evaluate changes in oxygenation as measured by pulse oximetry (SpO2) and saturated venous oxygenation (SvO2) during weaning from mechanical ventilator support. DESIGN Exploratory, pilot study. SETTING Cardiovascular intensive care unit in a private 691-bed acute care medical center in the South. SUBJECTS Ten adults between 50 and 76 years of age who had uncomplicated coronary artery bypass graft surgery. OUTCOME MEASURES SpO2 and SvO2 obtained at start of each weaning event and each minute for 5 minutes thereafter. METHOD Five discrete events associated with the unit's weaning protocol were studied: ventilator adjustments, continuous positive airway pressure trial, respiratory mechanics, removing continuous positive airway pressure and suctioning, and extubation. Weaning events, initiated by unit staff members, were based on subjects' arterial blood gases, SpO2, respiratory rate, blood pressure, heart rate, level of alertness, and respiratory effort. RESULTS Both SpO2 and SvO2 changed with weaning. For some subjects these changes were clinically important: SvO2 fell by 10% or more, and SpO2 fell to or below 90%. The assessment parameters guiding the weaning process resulted in some weaning events being initiated when SvO2 was at or below 60%. CONCLUSIONS Measures of SpO2 and SvO2 are sensitive to changes in oxygenation status during weaning. Although more study is needed, SvO2 measures provide valid information about oxygen status and can be used to guide weaning.