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A rapid outbreak of novel coronavirus, coronavirus disease‐2019 (COVID‐19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID‐19 patient mortality. The clinical data of 596 COVID‐19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID‐19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%–50%). Although the levels of C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID‐19 patients; CRP, ESR, and platelet‐to‐lymphocyte ratio (PLR) may not indicate the in‐hospital mortality of COVID‐19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32–19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in‐hospital mortality rate of this group was significantly higher than other COVID‐19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p =.00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome. [ABSTRACT FROM AUTHOR]