In recent years, the use of continuous positive airway pressure (CPAP) has gained immense popularity as the primary mode of respiratory support . CPAP use has been associated with the reduced need for mechanical ventilation and associated lung injury. CPAP improves ventilation- perfusion relationships and reduces oxygen requirements.However, failure of CPAP has variable incidence as shown in previous studies on predictors of CPAP failure which concluded ; gestational age <28 weeks, PROM, lack of exposure to antenatal steroids (ANS), product of CPAP pressure and FiO2 ≥1.28 , alveolar-arterial oxygen tension gradient (A-a DO2) >180 mmHg on the first arterial blood gas (ABG) and small for gestational age (SGA).We performed a prospective study on 100 preterm neonates who were initiated on nasal continuous positive airway (CPAP) for respiratory distress to predict causes leading to this failure.CPAP failed in 48.5% of the cases. Neonates with lower birth weight , higher FiO2 at initiation of CPAP and Product of CPAP pressure & FiO2 at initiation ≥ 2.45 were at higher rates of CPAP failure.However, in multivariate analysis, only sepsis was a statistically significant cause of CPAP failure. The odds ratio for CPAP failure in cases who have clinical sepsis are 11.1 times higher than in cases who do not have sepsis with Confidence Interval (3.2-38.5%). And therefore, clinical sepsis can be considered as an associated or risk factor for CPAP failure.