The global pandemic due to coronavirus disease 2019 (COVID-19) has posed an overall threat to modern medicine. The course of the disease is uncertain with varying forms of presentation that cannot be managed solely with clinical skills and vigor. Since its inception, laboratory medicine forms a backbone for the proper diagnosis, treatment, monitoring, and prediction of the severity of the disease. Clinical biochemistry, an integral component of laboratory medicine, has been an unsung hero in the disease prognosis and severity assessment in COVID-19. This review attempts to highlight the biomarkers which have shown a significant role and can be used in the identification, stratification, and prediction of disease severity in COVID-19 patients. It also highlights the basis of the use of these biomarkers in the disease course and their implications.