Abstract Background In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Finding markers that predict the prognosis of patients with severe COVID-19 are of great value. Methods In this single-center，retrospective study, 157 patients with severe COVID-19 were recruited from a consecutive series. After screening, a total of 105 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. Results The dominant symptoms observed in the study included fever on admission, cough, fatigue and shortness of breath. The most frequent comorbidities were hypertension and diabetes. Compared with patients with higher CD4+T cells level, patients with lower CD4+T cells level were older and were more frequently male. In terms of laboratory findings, lymphocyte percentage, lymphocyte absolute value, CD3+T cell count, CD4+T cell count, CD8+T cell count were significantly lower in low group than in high group. The case in-hospital death rate was significant higher in patients with lower CD4+T level than in those with higher CD4+T level. After adjusting for potential confounding factors, CD4+T cells count below normal values showed independent prognostic value for all-cause in-hospital death in patients with severe COVID-19. Conclusions In patients with severe COVID-19, lower CD4+T cells count are independently associated with an increased rate of in-hospital death.