Background <p>Preterm infants have reduced nephrons at birth and are exposed to hyperoxic environments. The objective was to examine the effects of hyperoxia on renal injury.</p> Methods <p>We utilized a mouse model of experimental moderate (60% O₂)-severe (100% O₂) bronchopulmonary dysplasia (BPD), obtaining kidney tissue on postnatal day 14. The number of glomeruli, glomerulus length, and Bowman’s capsule’s length were recorded. Cell death and expression of multiple biomarkers were assessed.</p> Results <p>Morphometric analyses showed a significant decrease in glomeruli in male and female mice from room air (RA) to 60% BPD. Bowman’s capsule length was significantly increased from RA to 100% BPD in female kidneys. TUNEL staining, cleaved caspase 3, and 9 expression revealed significantly increased cell death in the kidneys in the moderate and severe BPD models. There was increased expression of Angiopoietin-2 in male kidneys of the moderate BPD group, whereas Angiopoietin-1 and vascular endothelial growth factor were decreased in female mice. In the moderate BPD model, there was upregulation of nuclear factor-kappa B, transforming growth factor-β1, interleukin (IL)-6, and IL-1β in male and female mice.</p> Conclusion <p>We report here that there is significant renal injury and cell death in moderate and severe mouse models of experimental BPD.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Neonatal kidneys are still developing at birth.</p> </ItemContent> <ItemContent> <p>Hyperoxia exposure to the whole mouse also impacts the developing neonatal kidney.</p> </ItemContent> <ItemContent> <p>There is significant renal injury in moderate and severe mouse models of experimental BPD.</p> </ItemContent> <ItemContent> <p>This includes morphometric changes in the kidney tissue and increased cell death.</p> </ItemContent> <ItemContent> <p>In addition, there are significant alterations in the expression of vascular and inflammatory biomarkers.</p> </ItemContent> </UnorderedList></p>