Preterm infants have a reduced pulmonary diffusing capacity that has been invoked to explain rapid arterial O(2)-desaturation during apnea, despite little evidence to support this view. We explored the role of diffusion limitation on O(2)-desaturation during apnea by developing a mathematical model of gas exchange in which O(2) dynamically loads the blood traversing the pulmonary capillary. While normal diffusing capacity DL((O(2)) had negligible impact on apneic desaturation, reduced DL((O(2)) advanced the onset of desaturation during apnea. Unexpectedly, despite considerable diffusion limitation, its influence on O(2)-desaturation disappeared within 15s, because its impact in slowing alveolar O(2) depletion maintained a higher driving pressure for diffusion. In contrast, reduced DL((O(2)) substantially slowed reoxygenation following apnea. Our findings do not support the hypothesis that reduced DL((O(2)) explains the rapid apneic desaturation observed in preterm infants. Instead, the signature of reduced DL((O(2)) is a prolonged hypoxemia following apnea, potentially causing a persistence of hypoxic conditions when heart rate and cardiac workload reach a peak.