Clara cell protein (CC16) is an anti-inflammatory protein and a biomarker of pulmonary epithelial cells and alveolocapillary membrane injury in adults. We investigated whether low cord blood concentrations of CC16 are associated with the development of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants and the relationship between CC16 and its pro-inflammatory counterpart, the secretory phospholipase A(2) (sPLA(2)) enzyme. CC16 concentration, sPLA(2) activity and IL-6 concentration were measured in cord blood plasma from 79 preterm infants (25 controls, 37 infants who developed RDS and 17 infants who developed BPD). After adjustment for gestational age and Apgar score at 5 min, the CC16 concentration was lower in BPD infants than in preterm controls (p<0.01). sPLA(2) activity was similar in all groups and the IL-6 concentrations were increased in both RDS and BPD infants (p<0.01 and p<0.05, respectively, vs. controls). We conclude that low cord blood CC16 concentrations in preterm infants independently predict the development of BPD. Low CC16 levels may reflect early lung injury, which contributes to the severity of RDS and progress towards BPD. Future studies are needed to assess whether the early administration of recombinant human CC16 in preterm infants with low cord blood CC16 prevents the development of BPD.