Chronic pulmonary infection by Pseudomonas aeruginosa is observed in 50% of patients with cystic fibrosis and requires the use of recurrent intravenous therapy. A decrease of resting energy expenditure (REE) and an increase of physical activity (PA) after intravenous anti-P. aeruginosa therapy (IVAT) is observed while total energy expenditure (TEE) does not change. A decrease in the energetic cost of physical activity (ECPA) could be hypothesized but has never been studied. Our aim was to assess the evolution of ECPA after home IVAT in both standardized condition at hospital and in free-living condition twice before and after IVAT. Sixteen CF patients (nine boys, seven girls) chronically colonized by P. aeruginosa with a mean age of 12.1+/-2.3 years (range 7.1-14.6) were studied before and after IVAT. Each patient passed throughout a visit in hospital: weight, height and fat-free mass were measured. Then, energy expenditure (EE) measured by indirect calorimetry and heart rate (HR) were simultaneously recorded at different levels of PA: REE, and at different intensity of physical activities on a cycloergometer using an incremental increase of the power brake force. Physical activity energy expenditure (PAEE) was computed in laboratory condition using PAEE=EE-BEE (basal energy expenditure). Linear regression between PAEE and power brake force was fitted for each patient before and after IVAT. ECPA in standardized conditions was compared at different range of power brake force using area under the curve (AUC). After coming back at home, 24 h TEE using the heart rate monitoring technique and PA by triaxial accelerometry were simultaneously measured in free-living condition for 24 h during a school day. ECPA in free-living conditions was compared by the ratio PAEE:PA where PAEE=DEE-REE (DEE=daily energy expenditure). After IVAT, median AUC between 60 and 90 W in standardized condition decreased significantly by -15.4% (median 14.9, range 8.8-30.3 vs. median 12.6, range 8.5-17.6; P<0.05, Wilcoxon rank test) while the decrease for lower range of power work load did not reach significance. Spearman correlation was significant between variations of forced expiratory volume in 1 s and variation of AUC at 30-60 W before and after IVAT in standardized condition. In free-living conditions, ratio PAEE/PA did not vary significantly (median 3.4, range 1.6-6.4 vs. median 2.8, range 1.4-4.8; NS). Our data demonstrate a decrease of ECPA after IVAT in standardized conditions for moderate level of PA (60-90 W), but not in free-living conditions. The decrease of ECPA was probably due to a decrease in the energetic cost of breathing after IVAT, that is particularly relevant to promote PA in CF patients.