Background Dyslipidemia has been observed in patients with coronavirus disease 2019 (COVID‐19). This study aimed to investigate blood lipid profiles in patients with COVID‐19 and to explore their predictive values for COVID‐19 severity. Methods A total of 142 consecutive patients with COVID‐19 were included in this single‐center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID‐19 in comparison with 77 age‐ and gender‐matched healthy subjects, their predictive values for COVID‐19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves. Results There were 125 and 17 cases in the non‐severe and severe groups, respectively. Total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non‐severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID‐19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800–0.935, p < 0.001), along with interleukin‐6 (IL‐6) (adjusted OR: 1.097, 95% CI: 1.034–1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834–0.941); moreover, the risk model established using ApoA1 and IL‐6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932–0.995). Conclusion Blood lipid profiles in patients with COVID‐19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID‐19.

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