OBJECTIVE: Global health resources have faced huge challenges from the pandemic coronavirus disease 2019 (COVID-19) since December 2019. Numerous clinical reports have focused on the association of serum amyloid A (SAA) levels with severe COVID-19. However, a systematic analysis synthesizing these findings has not been performed. This meta-analysis aims to systematically review the role of SAA levels in distinguishing among patients with mild, severe, and critical COVID-19. MATERIALS AND METHODS: A comprehensive literature search was conducted in the PubMed, Embase, and Web of Science databases from the beginning of the COVID-19 outbreak to February 1, 2021. Two investigators independently reviewed suitable studies. Pooled standardized mean differences (SMDs), 95% confidence intervals (CIs), and correlation coefficients (r) were computed using a random-effects model. RESULTS: We included 19 of 317 titles identified by our search, involving a total of 1806 mild cases and 1529 severe cases. Compared with the mild group, the severe group had markedly higher SAA levels (SMD=1.155, 95% CI 0.89, 1.42). Subgroup analysis revealed that the SAA level differences between the severe group and the mild group were associated with age, sample size, and detection method. Sensitivity analyses showed the credibility and robustness of our results. In addition, in six studies involving 1144 patients with severe COVID-19 and 433 patients with critical COVID-19, SAA was significantly higher in patients with critical COVID-19 (SMD=0.476, 95% CI 0.13, 0.82). CONCLUSIONS: High circulating SAA levels were markedly associated with COVID-19 severity, especially for subjects aged less than 50 years, compared with patients with mild COVID-19. SAA concentrations were also significantly higher in patients with critical COVID-19 compared with those with severe COVID-19. Further studies in large cohorts are needed to confirm whether the SAA is a useful tool in discriminating among patients with stable COVID-19, those with acute exacerbations, and subjects without disease.