Rationale: Air trapping and airflow obstruction are being increasingly identified in infants with cystic fibrosis. These findings are commonly attributed to airway infection, inflammation, and mucus buildup. Objective: To learn if air trapping and airflow obstruction are present prior to the onset of airway infection and inflammation in cystic fibrosis. Methods: On the day they are born, cystic fibrosis piglets lack airway infection and inflammation. Therefore, we used newborn wild-type and cystic fibrosis piglets to assess air trapping, airway size, and lung volume with inspiratory and expiratory x-ray computed tomography scans. Micro-computed tomography scanning was used to assess more distal airway sizes. Airway resistance was determined with a mechanical ventilator. Mean linear intercept and alveolar surface area were determined using stereological methods. Measurements and Main Results: On the day they were born, cystic fibrosis piglets exhibited air trapping more frequently than wild-type piglets (75% vs. 12.5%, respectively). Moreover, newborn cystic fibrosis piglets had increased airway resistance that was accompanied by luminal size reduction in the trachea, mainstem bronchi, and proximal airways. In contrast, mean linear intercept length, alveolar surface area, and lung volume were similar between both genotypes. Conclusions: The presence of air trapping, airflow obstruction, and airway size reduction in newborn cystic fibrosis piglets, prior to the onset of airway infection, inflammation, and mucus accumulation, indicates that cystic fibrosis impacts airway development. Our findings suggest that early airflow obstruction and air trapping in infants with cystic fibrosis might, in part, be due to congenital airway abnormalities.