Oxygen saturation is the percentage of hemoglobin that is saturated with oxygen, converting it to oxyhemoglobin. Oxygen saturation is a critical part of the physical examination of children with congenital heart disease (CHD). The expected oxygen saturation of a patient with CHD depends on their anatomical lesion, their previous surgeries, and any additional pulmonary or systemic pathology that may derange their saturation. Oxygen saturation can be noninvasively measured using pulse oximetry. Pulse oximetry is based on the differential absorption of infrared and red light by oxyhemoglobin and deoxyhemoglobin, with the former absorbing more infrared than the latter. Pulse oximetry readings may be inaccurate in settings of low cardiac output, peripheral vasoconstriction, arrhythmia, hypothermia, and venous pulsations. The use of pulse oximetry in the care of a child with CHD begins with the newborn critical CHD screen. A failed screen indicates a need for further investigation, such as repeated pulse oximetry or echocardiography. The oxyhemoglobin dissociation curve may be used to estimate the partial pressure of oxygen in the blood at various oxygen saturations. It is also a marker of the affinity of hemoglobin for oxygen, with a right-shifted curve indicating a higher oxygen tension needed to saturate hemoglobin. This is a helpful adaptation of the body to situations of stress such as fever, acidosis, and hypercapnia. An understanding of these concepts is paramount for providers caring for patients with known or potential CHD in any setting to appropriately interpret and respond to abnormal saturations for each child.