Background: The situation of the corona virus disease 2019(COVID-19) continues to evolve, our study explored the significance of serum levels of Matrix Metalloproteinase 3 (MMP3) as a marker for patients with COVID-19. Methods: Sixty-two COVID-19 patients in the First Hospital of Hunan University of Chinese Medicine and Loudi Center for Diseases Prevention and Control, from January to March 2020, were sampled as the novel coronavirus pneumonia infected group. One hundred and thirty-one cases from the First Hospital of Hunan University of Chinese Medicine, including 67 healthy individuals and 64 non- COVID-19 inpatients, served as the non-infected group. Approximately every 5 d, sera from 20 cases were collected and analyzed thrice, using an automatic biochemical analyzer, to detect serum MMP3 concentrations. Following normality tests, differences in serum MMP3 levels between the infected and non-infected group were analyzed via SPSS (version 25.0) software, using the Wilcoxon rank sum test. Results: The MMP3 concentration was 44.44（23.46~72.12）ng/ml in the infected group and 32.42 (28.16~41.21）ng/ml in the non-infected group. The difference between the two groups was statistically significant (Z=-2.799, P=0.005<0.05). Serum MMP3 concentration, measured over three separate time points, were 55.98 (30.80~75.97) ng/ml, 34.84 (0.00~51.84) ng/ml, and 5.71 (0.00~40.46) ng/ml, respectively. Conclusion: Detection of serum MMP3 levels may play an important role in the development of therapeutic approaches for COVID-19 and may indicate the severity of disease.