Obstructive Sleep Apnoea (OSA) is a common sleep disorder in which the upper airway repetitively collapses during sleep leading to nocturnal oxygen desaturation and sleep fragmentation. OSA is associated with obesity and weight loss can improve OSA. However effectiveness of weight loss in reducing OSA is unpredictable. Craniofacial structure is also a risk factor for OSA. Upper airway space can be compromised and become collapsible by either a restricted facial skeleton or excess soft tissue deposition from obesity. Airway size can increase through reductions in local adipose tissue with weight loss. However it is unknown whether craniofacial size impacts on the weight loss response to OSA. We hypothesise that effectiveness of weight loss may depend on the size of the craniofacial skeleton surrounding the upper airway. Method: Obese men with OSA underwent a 6 month weight loss program and a CT scan of the head at baseline. The scan was analysed to obtain a volume of the maxillomandibular enclosure surrounding the airway. We assessed whether maxillomandibular enclosure volume (MEV) is a moderator of the relationship between weight loss and OSA reduction using linear regression analyses. Results: MEV was assessed in 45 men (age 47.2±9.4, BMI 34.0±2.8) with -7.4±4.4 kg weight loss. Weight loss (%∆kg) was only weakly related to change in OSA, measured by the Apnoea-Hypopnea Index [AHI], (r² = 0.12, p=0.021). Moderation analysis using an interaction term (%∆kg*MEV) improved the fit of the model, effectively doubling the explained variance (r² = 0.25, p = 0.007). The interaction between %∆kg and MEV was significant (B±SE -0.12±0.05, p = 0.02). Conclusion: Craniofacial size may have some impact on effectiveness of weight loss as an OSA treatment, although only 25% of the variance in OSA after weight loss was explained. Further work is needed to investigate the relationship between obesity and OSA.