Abstract: COVID-19 has caused a huge health crisis and incalculable damage worldwide. Emerging immune escaping mutants of the virus suggests that SARS-CoV-2 may be persistent in human society like the flu virus and become a long-lasting health threat. The control of SARS-CoV-2 transmission and the development of an effective treatment are imminent. Therefore, it is imperative to find appropriate biomarkers to indicate pathological and physiological. Proteins are performers of life functions and their abundance and modification status can directly reflect the immune status. Post-translational modifications such as glycosylation and phosphorylation have a great impact on the regulation of protein functions. In the studies of SARS, Zika, and H1N1, post-translational modified proteins have shown to be reliable biomarkers. In recent years, mass spectrometry-based proteomics has made great progress due to the development of mass spectrometry technology. A review of research strategies for mass spectrometry-based biomarkers, especially in the application of protein post-translational modifications, is important for the victory of human beings fighting the Covid-19 epidemic. This review summarized the current progress of mass spectrometry-based studies on the PTM status of SARS-CoV-2 viral proteins, particularly in glycosylation and phosphorylation aspect. The challenge and prospect of the application of mass spectrometry in this particular research area were outlined.