OBJECTIVES Existing assessments of the cost of Pseudomonas Aeruginosa (PA) infections among patients with cystic fibrosis (CF) in the United Kingdom (UK) are incomplete and outdated. Therefore, we sought to determine the cost of PA infections in CF patients in the UK from a societal perspective. METHODS We developed a prevalence-based model with data on age- and sex-specific PA prevalence, health care utilization, other (non-medical) components of care, and productivity for CF patients. Using data from the medical literature, practice guidelines, National Schedule of Reference unit costs, and expert panel input, the annual per capita and total UK costs were calculated. Direct medical and non-medical costs were calculated as the product of 1) the age-dependent probability that a care component is used, 2) the age-dependent number of units used, and 3) its unit price. Indirect costs were calculated based on time lost from paid labor (work productivity) and unpaid labor, i.e. providing/receiving care or household work (leisure time). RESULTS Mean total annual per capita cost in the UK for 2007 was £22,186 [ £12,945 (direct medical), £505 (direct non-medical), and £8,735 (indirect)]. Approximately 2,400 people in the UK have CF with PA; therefore, the total national cost is £52.8 million (M) [(£30.8M direct medical, £1.2M direct non-medical, and £20.8M indirect)]. Twenty percent of the direct medical costs (DMC) result from acute exacerbations with 58% resulting from chronic care of PA infections. CONCLUSIONS The economic burden of PA in CF patients is substantial. Inasmuch as 58% of this cost is for direct medical care and 39% for indirect costs (13% and 87% for work and leisure time lost respectively), the medical community, employers and patients should be attentive to policy or product innovations that can diminish the incidence and burden of PA in CF, specifically focusing on delaying chronic infection and preventing acute exacerbations.