We examined the association between elevated concentrations of 25 blood proteins in blood spots collected on postnatal d 1, 7, and 14 from infants <28 wk gestation who survived to 24 mo and the risk of two patterns of early lung disease i.e. early and persistent pulmonary dysfunction (EPPD) and normal early pulmonary function followed by pulmonary deterioration (PD). Thirty-eight percent (n = 347) of our cohort had PD, and 43% (n = 383) had EPPD. On postnatal d 14, elevated concentrations of two proteins (RANTES and VEGF) were associated with reduced risk of PD. Similarly, the risk of EPPD was also reduced if three proteins had elevated concentrations on postnatal d 14 (RANTES, MMP-1, and VEGF). In contrast, the risk of EPPD was increased if on d 14 two proteins had elevated concentrations (IL-8 and ICAM-1). Inflammation might influence the risk of EPPD and PD or be a consequence of lung damage or therapies to minimize lung dysfunction.