OBJECTIVE(S): Previous literature has established a high prevalence of upper airway obstruction in children with craniofacial abnormalities. This study aims to perform quantitative airway volume measurements in patients with craniofacial abnormalities and compare them to age and sex-matched controls. METHODS: We performed a retrospective review of the records of all children with craniofacial abnormalities who underwent head-and-neck computed tomography (CT) imaging at a single tertiary-care center between 1/1/13 and 12/31/20 using the ICD-10 codes Q75.1, Q75.4, and Q87.0. These patients were then matched by age and sex to patients with isolated craniosynostosis (Q75.0). CT scans were imported into Dolphin Imaging software, and airway volumes were measured for the nasal cavity, nasopharynx, oropharynx, and hypopharynx. The primary outcome was the total airway volume, defined as the sum of these measurements. RESULTS: Thirty subjects with craniofacial syndromes were matched to 30 patients with isolated craniosynostosis (controls). In both groups, 18 subjects (60%) were male (p = 0.99). The average ages for syndromic patients and controls were 12.1 and 12.9 months, respectively (p = 0.84). On average, the total airway volumes of syndromic patients were 25% lower than those of controls (p = 0.02). Syndromic patients had 39% smaller nasal cavity volumes (p < 0.001) and 32% smaller nasopharyngeal volumes (p < 0.01). Significant volume differences were not observed for the oropharynx or hypopharynx. CONCLUSION: We present a unique technique to measure airway volumes in patients with craniofacial abnormalities. These findings will help practitioners to further understand the anatomy and pathophysiology of disturbed breathing in children with craniofacial syndromes. LEVEL OF EVIDENCE: III Laryngoscope, 2023.