Cystic fibrosis (CF) is a progressive genetic disorder caused by mutations in a gene encoding the cystic fibrosis transmembrane regulator (CFTR) protein leading to persistent and difficult to treat lower airway infections. Multi-drug resistant Pseudomonas aeruginosa is becoming increasingly more common as a cause of pulmonary exacerbations, and newer agents such as ceftolozane/tazobactam (C/T) are being sought for treatment. There is currently little published data regarding its use in cystic fibrosis, particularly in the setting of reduced renal clearance. This report details the case of a 63-year-old female with cystic fibrosis and chronic kidney disease stage III (estimated creatinine clearance of 25-30 ml/min, Cockroft-Gault) who was successfully treated for a pulmonary exacerbation with C/T 3 g (2000 mg/1000 mg) infused intravenously every 8 h when the P. aeruginosa minimum inhibitory concentration (MIC) was elevated at 8 mcg/mL. Serum samples were collected to determine concentrations by a validated high-performance liquid chromatography assay. The steady state 1-hr post-infusion peak (Cmax) and trough (Cmin) concentrations for ceftolozane were 145.04 mcg/mL and 82.08 mcg/mL, and 15.93 mcg/mL and 3.20 mcg/mL for tazobactam, respectively. The patient's symptoms resolved and her lung function returned to baseline. She completed 14 days of therapy and tolerated the infusion well without any infusion-related or adverse events.