Based on large serum and plasma proteome studies, we generate the Charité Open Peptide Standard for Plasma Proteomics (OSPP), an open, versatile peptide internal standard for targeted and untargeted mass spectrometry-based proteomic studies. The OSPP includes 211 concentration-matched stable-isotope-labeled peptides selected for consistent quantification across a large number of plasma and serum proteome studies, and synthetic accessibility. We demonstrate the utility of OSPP in a COVID-19 inpatient cohort study for improving analytical performances, for cross-platform alignment of proteomic data, disease stratification, and biomarker discovery.