Rationale: The effect of obesity on upper airway soft tissue structure and size was examined in the New Zealand Obese mouse (NZO) and in a control lean mouse, the New Zealand White (NZW). Objectives: We hypothesized that the NZO mouse has increased volume of neck fat and upper airway soft tissues and decreased pharyngeal airway caliber. Methods: Pharyngeal airway size, volume of the upper airway soft tissue structures and distribution of fat in the neck and body were measured using magnetic resonance imaging (MRI). Dynamic MRI was used to examine the differences in upper airway caliber between inspiration and expiration in NZO vs. NZW mice. Measurements and Main Results: The data support the hypothesis that in the obese NZO vs. lean NZW mice; airway caliber was significantly smaller (p < 0.03), with greater parapharyngeal fat pad volumes (p < 0.0001) and greater volume of other upper airway soft tissue structures (tongue, p = 0.003; lateral pharyngeal walls, p = 0.01; soft palate, p = 0.02). Dynamic MRI showed that the airway of the obese NZO mouse dilated during inspiration, while in the lean NZW, the upper airway was reduced in size during inspiration. Conclusions: In addition to increased volume of pharyngeal soft tissue structures, direct fat deposits within the tongue may contribute to airway compromise in obesity. Pharyngeal airway dilation during inspiration in NZO mice compared to narrowing in NZW mice suggests that airway compromise in obese mice may lead to muscle activation to defend upper airway patency during inspiration.