Updated project metadata. Inactivity and unloading. induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. We used mass spectrometry-based proteomics to measure the abundance changes of proteins circulating in the blood plasma of young healthy subject undergoing ten days of continuous bed rest. Several plasma components, such as the complement cascade and lipid carriers, and proteins derived from the extracellular matrix and tissue leakage, such as lumican and teneurin-4, changed their abundance at different loading states of the body. Searching for potential plasma biomarkers relaying changes in muscle trophism, we identify common proteomic signatures distinguishing the majority of subjects undergoing extensive unloading-mediated muscle atrophy from those largely maintaining their initial muscle mass at the end of bed rest. Some of these plasma proteins also have different abundance in the serum proteome of cancer patients developing cachexia compared to that of healthy controls. Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions.