Neonatal Respiratory Distress Syndrome (RDS) remains among the leading causes of morbidity and mortality in preterm and low birth weight infants. Treatment with mechanical ventilation and early administration of exogeneous surfactant improve outcomes. RDS severity impacts ventilation duration and surfactant dosing, increasing the risk of associated side effects. Better markers are required to predict disease course and determine which neonates could benefit from early, aggressive treatment. In our study we have shown how T cell marker T cell Receptor Excision Circles (TREC), quantified shortly after birth, can predict RDS severity in preterm and very low birth weight infants. TREC copy numbers are significantly lower in neonates who go on to develop severe RDS when compared to those who will suffer from no or mild RDS. This trend persists when accounting for confounders such as gestational age and birth weight. Our findings suggest that TREC could potentially serve as a reliable biomarker for assessing RDS disease severity, thus dictating the timely and appropriate management of Neonatal RDS.