In this study, we achieved a global view of Cu-responsive changes in the prokaryotic model organism Rhodobacter capsulatus using label-free quantitative differential proteomics. Semi-aerobically grown cells under heterotrophic conditions in minimal medium (~ 0.3 M Cu, optimal for growth) were compared with cells grown similarly but supplemented with either 5 M Cu or with 5 mM of the Cu-chelator bathocuproine sulfonate. Mass spectrometry based bottom-up proteome analyses of unfractionated cell lysates identified with high confidence 2430 of the 3632 putative proteins encoded by the genome.