Severe acute respiratory syndrome coronavirus 2 infections are uncommon in newborn infants. This report describes possible in utero transmission of the B.1.1.7 (alpha) variant in a preterm infant born at 31 weeks' gestational age who presented with severe respiratory disease. The infant was treated with high-frequency oscillatory ventilation, antiviral medications, and corticosteroids and transitioned to noninvasive respiratory support on day 33. By day 63, she was off positive pressure support and breathing room air and she was discharged from the hospital on day 70. She demonstrated normal growth and development at a 6-month follow-up visit. Placental histopathology revealed placentitis characterized by loss of intervillous spaces resulting from fibrin deposition and inflammatory cell infiltration. Optimum management strategies for treating infants with severe acute respiratory syndrome coronavirus 2 infection have yet to be determined.