Objective This study aims to investigate the prognostic significance of inflammatory cytokines and lymphocyte levels in predicting disease progression among patients with COVID-19 infection.Methods Ninety-two hospitalized COVID-19 patients were retrospectively included as subjects for this study. General clinical information and various indicators, including lymphocyte count, interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor (TNF), were collected. All patients received treatment according to the ninth edition of the guidelines for COVID-19. Incidences of endotracheal intubation and mortality within 28 days were observed.Results 1.Lymphocyte count and inflammatory factors demonstrated predictive value for endotracheal intubation in COVID-19 patients. The critical lymphocyte count value was 0.91, with a sensitivity of 38.8%, specificity of 92.9%, and AUC of 0.687 (95% CI: 0.580–0.795). The critical IL-6 value was 38.21, with a sensitivity of 81%, specificity of 63.3%, and AUC of 0.771 (95% CI: 0.6670.872). The critical IL-8 value was 54.09, with a sensitivity of 61.9%, specificity of 75.5%, and AUC of 0.665 (95% CI: 0.545–0.771). The critical IL-10 value was 5.05, with a sensitivity of 71.4%, specificity of 65.3%, and AUC of 0.712 (95% CI: 0.601–0.813). The tumor necrosis factor cutoff was 1.98, with a sensitivity of 52.4%, specificity of 73.5%, and AUC of 0.648 (95% CI: 0.530–0.756). 2.Lymphocyte count and inflammatory factors also exhibited predictive value for death in COVID-19 patients. The critical lymphocyte count value was 0.56, with a sensitivity of 71.2%, specificity of 57.5%, and AUC of 0.641 (95% CI: 0.528–0.754). The critical IL-6 value was 53.05, with a sensitivity of 75%, specificity of 71.2%, and AUC of 0.770 (95% CI: 0.6690.870). The critical IL-8 value was 54.09, with a sensitivity of 62.5%, specificity of 63.5%, and AUC of 0.687 (95% CI: 0.5780.796). The critical IL-10 value was 5.05, with a sensitivity of 70%, specificity of 63.5%, and AUC of 0.683 (95% CI: 0.5740.792). The tumor necrosis factor cutoff was 0.98, with a sensitivity of 90%, specificity of 34.6%, and AUC of 0.636 (95% CI: 0.523–0.749).Conclusion Elevated inflammatory factors and decreased lymphocyte levels have prognostic value for predicting endotracheal intubation and mortality in COVID-19 patients, providing valuable insights for clinicians in anticipating disease progression.