Background To analyse the clinical characteristics, laboratory tests, and imaging findings of severe cases of coronavirus disease 2019 (COVID-19) versus severe cases of influenza A (H1N1).Methods We retrospectively analysed the clinical data of moderate and severe COVID-19 and H1N1 cases between January 23 and February 23, 2020.Results A total of 33 COVID-19 cases had a clear history of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with an incubation period of 11.12 ± 7.47 days. A total of 29 H1N1 cases were included in this study. Most cases were sporadic, with an incubation period of 3.67 ± 0.82 days (P = 0.002). The age at onset was 19.79 ± 23.88 years for H1N1 and 43.48 ± 17.82 years for COVID-19 (P < 0.001). For H1N1, common clinical symptoms were high fever and myalgia. The time of disease progression from moderate to severe was 13.60 ± 5.64 days for COVID-19 and 5.25 ± 2.36 days for H1N1 (P = 0.035). Laboratory tests showed that white blood cells (WBC), neutrophils (N), lactate dehydrogenase (LDH), C-reactive protein (CPR), and procalcitonin (PCT) were significantly higher in severe H1N1 cases than in severe COVID-19 cases. D-dimer (DD) was 1.43 ± 1.19 µg/mL in the COVID-19 group, which was higher than that in the H1N1 group (0.88 ± 0.32 µg/mL, P = 0.013). High-resolution computed tomography (CT) showed severe COVID-19 cases presented mainly interstitial involvement, shown by large ground-glass opacities, whereas severe H1N1 cases presented both interstitial and parenchymal involvement, especially parenchymal involvement. All the COVID-19 patients survived to discharge, and one H1N1 patient died.Conclusion Compared with H1N1 patients, COVID-19 patients had a clear history of exposure to SARS-CoV-2, were older, presented milder clinical symptoms and a slower progression, and rarely had bacterial infections. Most H1N1 patients had sporadic H1N1 with an acute onset, high fever, and rapid progression; secondary bacterial infection was an important cause of disease aggravation.