Background: For coronavirus disease 2019 (COVID-19), early identification of patients with serious symptoms at risk of critical illness and death is important for personalized treatment and balancing medical resources. Methods: Demographics, clinical characteristics, and laboratory tests data from 726 patients with serious COVID-19 at Tongji Hospital (Wuhan, China) were analyzed. Patients were classified into critical group (n = 174) and severe group (n= 552), the critical group was sub-divided into survivors (n = 47) and non-survivors (n = 127). Results: Multivariable analyses revealed the risk factors associated with critical illness in serious patients were: Advanced age, high respiratory rate (RR), high lactate dehydrogenase (LDH) level, high hypersensitive cardiac troponin I (hs-cTnI) level, and thrombocytopenia on admission. High hs-cTnI level was the independent risk factor of mortality among critically ill patients in the unadjusted and adjusted models. ROC curves demonstrated that hs-cTnI and LDH were predictive factors for critical illness in patients with serious COVID-19 whereas procalcitonin and D-Dimer with hs-cTnI and LDH were predictive parameters in mortality risk. Conclusions: Advanced age, high RR, LDH, hs-cTnI, and thrombocytopenia, constitute risk factors for critical illness among patients with serious COVID-19, and the hs-cTnI level helps predict fatal outcomes in critically ill patients.