OBJECTIVE: To evaluate the efficacy of hypoxic gas therapy using nitrogen, where the fraction of inspired oxygen (Fio2) was reduced to <0.21 in patients with univentricular parallel circulation. DESIGN: Case report. SETTING: A pediatric intensive care unit at a university hospital. PATIENTS: Two neonatal patients with hypoplastic left heart syndrome admitted to the pediatric intensive care unit preoperatively. INTERVENTIONS: Nitrogen insufflation by using continuous-flow respiratory support. MEASUREMENTS AND MAIN RESULTS: We reduced the Fio2 in these patients by giving additional nitrogen to relieve pulmonary overcirculation and systemic hypoperfusion suspected by transcutaneous arterial oxygen saturation >90%, systemic arterial hypotension, and low urine output in the preoperative course. The improvement of systemic hemodynamics concomitant with decreases in transcutaneous arterial oxygen saturation <85% was accomplished by controlling Fio2 between 0.14 and 0.18. These infants were able to undergo Norwood's surgery after several days without complications relating to Fio2 reduction. CONCLUSION: Hypoxic gas therapy with nitrogen was effective clinically in preventing pulmonary overcirculation in neonatal patients with univentricular and parallel circulation.