Although blood plasma inherently contains protein biomarkers for human disease diagnosis, their determination is difficult since more than 3700 proteins are commonly present. The associated protein-separation problem can, however, be dramatically simplified by analyzing plasma for a subproteome, such as those proteins that contain bound metals. To this end, the analysis of plasma by size-exclusion chromatography (SEC) coupled with an inductively coupled plasma atomic-emission spectrometer (ICP-AES), which served as the simultaneous Cu-, Fe- and Zn-specific detector, revealed the presence of approximately 12 metalloproteins within 25 min. In the context of modern proteomics research, SEC-ICP-AES therefore represents a viable proteomic approach that can be applied to diagnose human diseases that are associated with increased or decreased concentrations of certain plasma metalloproteins. Furthermore, SEC-ICP-AES can be employed to probe the effect of environmental chemicals or drugs in blood at the metalloprotein level, which makes it a versatile research tool for applications in toxicology, applied medicine, pharmacology and nutritional science.