Objectives: This study aims to investigate the risk factors associated with severity and death from COVID-19 through a systematic review and meta-analysis of the published documents in Iran. Methods: A systematic search was performed based on all articles indexed in Scopus, Embase, Web of Science (WOS), PubMed, and Google Scholar in English and Scientific Information Database (SID) and Iranian Research Institute for Information Science and Technology (IRA)NDOC indexes in Persian. To assess quality, we used the Newcastle Ottawa Scale. Publication bias was assessed using Egger's tests. Forest plots were used for a graphical description of the results. We used HRs, and ORs reported for the association between risk factors and COVID-19 severity and death. Results: Sixty-nine studies were included in the meta-analysis, of which 62 and 13 had assessed risk factors for death and severity, respectively. The results showed a significant association between death from COVID-19 and age, male gender, diabetes, hypertension, cardiovascular disease (CVD), cerebrovascular disease, chronic kidney disease (CKD), Headache, and Dyspnea. We observed a significant association between increased white blood cell (WBC), decreased Lymphocyte, increased blood urea nitrogen (BUN), increased creatinine, vitamin D deficiency, and death from COVID-19. There was only a significant relationship between CVD and disease severity. Conclusion: It is recommended that the predictive risk factors of COVID-19 severity and death mentioned in this study to be used for therapeutic and health interventions, to update clinical guidelines and determine patients’ prognoses.