Background Neonatal mortality accounts for 47% of under-five deaths globally, with neonates representing two-thirds of pediatric admissions in Kenya. Respiratory distress (RD) is a major cause of neonatal morbidity and mortality, and Continuous Positive Airway Pressure (CPAP) is recommended as an effective intervention in low- and middle-income countries (LMICs). This study assessed CPAP uptake, short-term outcomes, and barriers to its utilization in three county hospitals in Nairobi, Kenya. A mixed-methods study was conducted in three county hospitals. The quantitative component was an analytical cross-sectional study carried out from 13 September to 10 October 2023, assessing CPAP uptake and short-term outcomes among 178 neonates, including length of hospital stay, oxygen therapy duration, mortality, referral for ventilatory support, and adverse events. Qualitative data were collected between 13 and 27 September 2023 using piloted key informant and in-depth interviews with 22 healthcare workers to explore barriers to CPAP use, such as equipment limitations, infrastructure gaps, and staffing constraints. Among 178 neonates, CPAP uptake was 57.3%, with respiratory distress syndrome being the most common indication. The CPAP group had a higher discharge proportion (78.43%, p=0.0242). Adverse events among discharged neonates included nasal trauma (2.81%) and pneumothorax (0.56%). The CPAP group also had shorter oxygen therapy duration and significantly lower mortality compared to the oxygen therapy group. Multivariate analysis adjusted for potential confounders; however, disease severity was not correlated with mortality. Qualitative findings identified key barriers to optimal CPAP use, including limited equipment, poor infrastructure, inadequate family involvement, and workforce gaps. CPAP demonstrated favorable short-term outcomes, including reduced oxygen duration and lower mortality. However, interpretation across illness severities is limited by the lack of severity-adjusted analyses. Addressing persistent barriers—particularly equipment shortages, infrastructure limitations, inadequate family-centred care, and staffing challenges—is essential to strengthening CPAP implementation and improving neonatal outcomes in LMIC settings.