Obstructive sleep apnoea is a common condition associated with cardiovascular risk. Continuous positive airway pressure (CPAP) is an effective treatment but is associated with nasal side-effects, which hinder compliance and may result from inflammation. We investigated whether CPAP was pro-inflammatory to human subjects in vivo, and to cultured bronchial epithelial cells in vitro. In vivo, we further investigated whether induction of nasal inflammation was associated with the development of systemic inflammation, nasal symptoms and changes in nasal mucociliary clearance. In vitro, CPAP resulted in cytokine release from cultured BEAS-2B cells in a time- and dose (pressure)-dependent manner. In vivo, CPAP resulted in dose-dependent upregulation of nasal inflammatory markers associated with the development of nasal symptoms, and reduced mucociliary clearance. CPAP also upregulated selected markers of systemic inflammation. CPAP results in dose-dependent release of inflammatory cytokines from human epithelial cells in vitro and in vivo. In vivo responses were associated with systemic inflammation, reductions in nasal mucociliary function and the development of nasal symptoms. This emphasises the need for novel strategies to reduce nasal inflammation and therefore aid compliance.