Pulmonary rehabilitation can improve the functional capacity, but has a variable effect on the low fat free mass (FFM) in patients with COPD. We hypothesised that pulmonary rehabilitation would not affect catabolic drives such as systemic inflammation and also protein breakdown. Patients (n=40) were studied at the commencement of an 8- week in-patient pulmonary rehabilitation programme, at the end and four weeks later. FFM and functional capacity (quadriceps strength, handgrip strength and peak workload) were assessed. Pseudouridine (PSU) urinary excretion (cellular protein breakdown) and inflammatory status were determined. Healthy subjects had a single baseline assessment (n=18). PSU, IL-6 and sTNF-alphaR75 were elevated in patients compared with healthy subjects while FFM and functional capacity were reduced, all p<0.01. PSU was inversely related to both FFM and skeletal muscle function. FFM and functional parameters increased with rehabilitation, but PSU and inflammatory status were unaffected. The gain in FFM was lost four weeks after the completion of rehabilitation, p<0.01. The anabolic effect of pulmonary rehabilitation improved FFM but it did not reverse the elevated protein breakdown or systemic inflammation. Thus on cessation of pulmonary rehabilitation the FFM gains were lost due to a loss of anabolic drive.