OBJECTIVE: To validate the hypothesis that fat tissue accumulation adjacent to the upper airway contributes to a predisposition to obstructive sleep apnea (OSA), irrespective of body mass index (BMI), as well as investigate the effect of the volume of fat tissue on pharyngeal mechanical loads. METHODS: Fourteen subjects and 14 controls were enrolled in this study. Pharyngeal anatomy (the fat tissue volume in the retropalatal region and retroglossal region) were evaluated using magnetic resonance imaging. Whether the subjects had a segmental closing pressure higher than atmospheric pressure was determined by pharyngoscopy under general anesthesia. The difference in fat tissue distribution between subjects with OSA and BMI-matched controls was investigated. Fat tissue distributions in subjects with positive or negative segmental closing pressure were also compared. RESULTS: Significant differences occurred between controls and subjects with OSA in volumes of parapharyngeal fat pad (P = .001), fat of soft palate (P = .01), as well as proportion of the parapharyngeal fat pad to the volume of total lateral pharyngeal soft tissues (P = .004). The volume of pharyngeal cavity, neck circumference, and volume of subcutaneous fat tissues were not significantly different statistically. Volume of fat in soft palate (odds ratio 5.893) and parapharyngeal fat pad in retropalatal and retroglossal region (odds ratios 1.781 and 1.845) were significant predictors of OSA. The volume of fat in the soft palate (P = .003) and parapharyngeal fat pad (P = .002) was higher in participants with positive retropalatal closing pressure; participants with positive retroglossal closing pressure had increased volumes of the tongue (P = .02) and the parapharyngeal fat pad (P = .004). CONCLUSIONS: Patients with OSA have more fat tissue adjacent to the pharyngeal cavity than BMI-matched controls. Fats deposited around the upper airway may contribute to the collapsibility of retropalatal and retroglossal airway in both patients and controls.