Persistent pulmonary hypertension of the newborn is a clinical condition with a low global incidence (2 to 4 per 1000 live births), predominant in premature and post-term infants, yet with significant mortality (up to 33%). The comprehensive management of this syndrome, characterized by persistent and severe hypoxemia due to failure in fetal circulation transitioning to extrauterine life, poses a real challenge in low and middle-income countries. This is primarily due to limited availability and high costs of first-line therapies such as nitric oxide once the diagnosis is established. We present a case from a referral institution in Barranquilla, Colombia, of a 32-week male newborn with early neonatal sepsis, hyaline membrane disease, and marked clinical deterioration, diagnosed with pulmonary hypertension by echocardiography. He was managed with nitric oxide and simultaneous high-frequency mechanical ventilation for 24 hours, showing an adequate response.Additionally, a phosphodiesterase type 5 inhibitor and inodilator were adjunctively administered, resulting in subsequent reduction and normalization of pulmonary pressure.