Mass spectrometry (MS) is one of the key technologies used in proteomics. In recent years, MS has been used extensively for the identification of proteins in complex biological samples. Consequently, a majority of studies of human samples studied using proteomics have focused on identifying human proteins in samples such as human plasma to pin down prognostic or diagnostic biomarkers associated with particular conditions or diseases. The current study aims to investigate the presence of microbial (viral and bacterial) proteins in healthy human plasma samples, along with applying the strategy to mine for SARS-CoV-2 related proteins in SARS-CoV-2 samples. To accomplish the objective of the project, the trans-proteomics pipeline (TPP) was used to execute the analysis by translating the raw MS proteomic data of healthy human plasma into a microbial protein list. The study uncovered the presence of a number of bacterial and viral proteins in the human plasma. Also, the study was able to characterize the microbial proteomic profile of the human plasma of SARS-CoV-2 patients at different degrees of severity. It was found that 42% of the overall identified microbial peptides is exclusive to the plasma of deceased subjects. The strategy will help in developing diagnostic tests for infectious and cancerous diseases based on the presence and absence of microbial biomarkers in human samples.