Exposure to hyperoxemia from excessive oxygen supplementation and episodes of intermittent hypoxemia have been associated with damage to the eye, lung, and central nervous system in premature infants. The inherent respiratory instability of the premature infant combined with limited staffing or equipment resources often affect SpO₂ targeting and increase exposure to extreme SpO₂ levels. Multiple systems for closed loop control of inspired oxygen have been developed to improve SpO₂ targeting. This article reviews the evidence provided by clinical studies evaluating the efficacy of these systems in extreme premature infants.