Background: Coronavirus disease-2019 (COVID-19) has spread all over the world and brought extremely huge losses. There is no study to systematically analyse the features of hydroxybutyrate dehydrogenase (α-HBDH) in COVID-19 patients during the periods before and after illness progression, before death and course from exposure onset. Methods: We collected all included patients' general information, clinical type, α-HBDH value and outcome, and analyzed α-HBDH values within different initial time and different periods. Results: In the first 30 days after symptom onset, the α-HBDH median value was 156.33 U/L. The first test of α-HBDH since exposure onset appeared on the 8th day, it increased from the 8th day to 18th day and decreased after the 18th day. α-HBDH median value showed a slight change until it started to increase 1 day before transforming to severe type, while it continued to increase during 4 days before and after transforming to critical type. The α-HBDH median value ranged from 191.11 U/L to 455.11U/L before death. Conclusions: α-HBDH value increases in some COVID-19 patients, obviously in severe type, critical type and death patients, and mainly in 18 days after exposure onset and 10 days after symptom onset. α-HBDH increases 1 day before transforming to severe type, continues to increase in critical type and death patients, increases rapidly 5 days before death. The increase of α-HBDH suggests that COVID-19 patients have tissues and organs damage, mainly in heart. In brief, α-HBDH is an important indicator to judge the severity and prognosis of COVID-19.