the benefit on the number of identified proteins is well documented and the depletion step remains widely used in in-depth proteomics. Recently, single-use depletion spin columns have been developed (i.e High Select™ Top14 Abundant Protein Depletion Mini Spin Columns, Thermo) which greatly reduces the handling time compared to HPLC columns and enables parallel depletion of multiple samples which has not been possible in the previous multiple use columns. The covid-19 pandemic also shed light on the need of a depletion protocol easily adapted in a BSL3 facility without needs for special equipment such as an HPLC system, as heat inactivation of the virus prior to depletion could affect the depletion efficacy. The aim of this study was to evaluate the use of single-use spin columns for high abundant protein depletion prior to in-depth MS based global plasma analysis, to improve throughput while maintaining high proteome coverage and high reproducibility.