Abstract: Objective To investigate the differences of cytokine profiles between patients with novel COVID-19 and bacterial pneumonia, unravel the immunopathological mechanism of COVID-19, and provide evidence for new therapeutic targets in COVID-19. Methods In this study, 15 serum samples were collected from mild COVID-19 patients （COVID-19 group）, bacterial pneumonia patients （bacterial pneumonia group）, and healthy controls （healthy control group）, respectively. The expression profile of 48 cytokines was determined to clarify the differences among three groups. The expression levels of 48 cytokines at different time points were measured in serum samples from 10 patients with COVID-19 to analyze their correlation with clinical features and disease progression. Results In the comparation between the COVID-19 group and the bacterial pneumonia group, the expression levels of MIF, GROα, GM-CSF and TNF-β were upregulated in COVID-19 patients（all P < 0.05）, whereas those of IL-10, IL-18, IL-2Rα and MIG were upregulated in patients with bacterial pneumonia（all P < 0.05）. The expression level of M-CSF was significantly downregulated in COVID-19 patients at the second week of hospitalization. The changes in the expression level of MCP-1 were consistent with the nucleic acid test results of COVID-19 patients. Conclusions The cytokine profiles differ between patients with COVID-19 and bacterial pneumonia. In addition, M-CSF and MCP-1 play critical roles in the progression of COVID-19.