Objective To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). Methods The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. Results The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z 1 = − 1.426, P = 0.154. The Z 1 values (Z 1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were − 5.569, − 6.967, and − 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. Conclusion SAA can be used as a predictor of the prognosis in patients with COVID-19.