In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 versus 46.5 ± 14.7, p<0.001), cytokeratin-19 fragment (CYFRA21-1) (2.2 ± 0.9 versus 1.9 ± 0.8, p<0.001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 versus 2.1 ± 1.2, p<0.001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 versus 10.5 ± 4.6, p<0.001) and 153 (14.4 ± 8.9 versus 10.1 ± 4.4, p<0.001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1 and CA125: p<0.001; CEA and CA153: p<0.01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (p<0.01). There were positive associations between levels of C-reactive protein and levels of HE4 (R= 0.631, p<0.001), CYFRA21-1(R= 0.431, p<0.001), CEA (R= 0.316, p<0.001), SCC (R= 0.351, p<0.001), CA153 (R= 0.359, p<0.001) and CA125 (R= 0.223, p=0.031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute lung injuries. This article is protected by copyright. All rights reserved.