Background and aims Creatine kinase (CK), a marker of muscle damage, is potentially associated with a more severe COVID-19 . In this systematic review and meta-analysis, we aim to evaluate the association between the elevated CK and severity and mortality in COVID-19 . Methods We performed a systematic literature search on PubMed, Scopus, and Embase up until January 26 , 2020 . The main outcome was poor outcome, a composite of mortality and severe COVID-19 . Results There are 2471 patients from 14 studies included in this systematic review and meta-analysis . The incidence of elevated CK in this pooled analysis was 17% (11% , 22 %) and the incidence of poor outcome in this pooled analysis was 27% (19% , 34 %). Elevated CK was associated with poor outcome in patients with COVID-19 (OR 3.01 [2.21 , 4.10], p <0.001; I2 : 10.2 %). The effect estimate did not vary with age (p = 0.610), male (p = 0.449), hypertension (p = 0.490), and diabetes (p = 0.457). Elevated CK has a sensitivity of 0.24 (0.17 , 0.32), specificity of 0.91 (0.86 , 0.94), PLR of 2.6 (1.9 , 3.7), NLR of 0.84 (0.78 , 0.90), DOR of 3 (2 , 5), and AUC of 0.62 (0.57 , 0.66) for predicting poor outcome in patients with COVID-19 . In this pooled analysis, elevated CK confers to a 49% probability for poor outcome and a non-elevated CK confers to a 24% probability . Subgroup analysis and univariate meta-regression indicates that the sensitivity and specificity does not vary with age, male, hypertension, and diabetes . Conclusion Elevated CK was associated with increased mortality and severity in patients with COVID-19. PROSPERO CRD42021233435.