Rationale. Diaphragm thickness is increased in cystic fibrosis, but it shows a marked variability between patients. The variable response of the diaphragm to loading may reflect the combined and opposite effects of training by the respiratory disease and systemic inflammation. Objectives. To assess the impact of systemic inflammation on diaphragm and limb muscle strength and bulk in adult patients with cystic fibrosis. Methods. In 38 stable cystic fibrosis patients and 20 matched controls, we measured fat free mass, inspiratory muscle strength, diaphragm thickness, quadriceps and biceps strength and cross-sectional area, and circulating levels of leukocytes, C-Reactive Protein, Interleukin-6, -8, -17, Tumor Necrosis Factor-, Tumor Necrosis Factor- soluble receptors, and immunoglobulin G. Measurements and Main Results. Patients had increases in several inflammatory markers that correlated with the severity of lung disease and nutritional depletion. Compared to controls, patients had increased diaphragm thickness and inspiratory muscle strength, and a trend toward a reduction in limb muscle strength and bulk. Multiple regression analyses identified fat free mass and airway resistance as independent predictors of diaphragm thickness, but systemic inflammation had no (or only a minor) predictive effect on fat free mass, inspiratory muscle strength, diaphragm thickness, and limb muscle strength and bulk. Conclusions. In patients with cystic fibrosis, the intensity of systemic inflammation does not account significantly for the variance of fat free mass, and diaphragm or limb muscle strength and bulk. Training of the diaphragm in cystic fibrosis occurs despite the presence of systemic inflammation.