With the surge in the prevalence of coronavirus disease (COVID-19) in Beijing starting in October 2022, hospitalisations have increased markedly. The present study aimed to evaluate factors associated with in-hospital mortality in patients with COVID-19. Using data from hospitalised patients, sex differences in clinical characteristics, in-hospital management, and in-hospital mortality among patients diagnosed with COVID-19 were evaluated. Additionally, predictive factors associated with mortality in 1091 patients, who were admitted to the Beijing Anzhen Hospital (Beijing, China) for COVID-19 between October 2022 and January 2023, were also evaluated. Data from 1091 patients hospitalised with COVID-19 were included in the analysis. The in-hospital mortality rates were 14.9% and 10.4% for males and females, respectively. Multifactorial logistic analysis revealed that lymphocyte percentage (LYM%) (odds ratio [OR] 0.863 [95% confidence interval (CI) 0.805-0.925]; P<0.001), uric acid (OR 1.004 [95% CI 1.002-1.006]; P=0.001), and high-sensitivity C-reactive protein (hs-CRP) (OR 1.094 [95% CI 1.012-1.183]; P=0.024) were independently associated with in-hospital mortality from COVID-19. Among female patients, multifactorial analysis revealed that LYM% (OR 0.856 [95% CI 0.796-0.920]; P<0.001), older age (OR 1.061 [95% CI 1.020-1.103]; P=0.003), obesity (OR 2.590 [95% CI 1.131-5.931]; P=0.024), and high high-sensitivity troponin I level (OR 2.602 [95% CI 1.157-5.853]; P=0.021) were risk factors for in-hospital mortality. Receiver operating characteristic (ROC) curve analysis revealed that the efficacy of LYM% in predicting in-hospital death and its area under the ROC curve (AUC) for predicting in-hospital death in males was 0.800, with a sensitivity of 63.2% and specificity of 83.2%. The AUC for predicting hospital death in females was 0.815, with a sensitivity of 87.5% and specificity of 64.4%. LYM% was a consistent predictor of in-hospital mortality in both sexes. Older age and markers of systemic inflammation, myocardial injury, and metabolic dysregulation were also associated with higher mortality risk. These findings may help identify patients who require closer monitoring and tailored interventions to improve outcomes.