Sepsis has emerged as a major global public health concern due to its elevated mortality and high cost of care. This study aimed to evaluate the risk factors associated with the mortality of sepsis patients in the Intensive Care Unit (ICU), and to intervene in the early stages of sepsis in order to improve patient outcomes and reduce mortality. From January 1st, 2021 to December 31st, 2021, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Huashan Hospital Affiliated to Fudan University, and The Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine were designated as sentinel hospitals, and sepsis patients in their respective ICU and Emergency ICU were selected as research subjects, and divided into survivors and non-survivors according to their discharge outcomes. The mortality risk of sepsis patients was subsequently analyzed by logistic regression. A total of 176 patients with sepsis were included, of which 130 (73.9%) were survivors and 46 (26.1%) were non-survivors. Factors identified as having an impact on death among sepsis patients included female [Odds Ratio (OR) = 5.135, 95% confidence interval (CI): 1.709, 15.427, P = .004)], cardiovascular disease (OR = 6.272, 95% CI: 1.828, 21.518, P = .004), cerebrovascular disease (OR = 3.133, 95% CI: 1.093, 8.981, P = .034), pulmonary infections (OR = 6.700, 95% CI: 1.744, 25.748, P = .006), use of vasopressors (OR = 34.085, 95% CI: 10.452, 111.155, P < .001), WBC < 3.5 × 109/L (OR = 9.752, 95% CI: 1.386, 68.620, P = .022), ALT < 7 U/L (OR = 7.672, 95% CI: 1.263, 46.594, P = .027), ALT > 40 U/L (OR = 3.343, 95% CI: 1.097, 10.185, P = .034). Gender, cardiovascular disease, cerebrovascular disease, pulmonary infections, the use of vasopressors, WBC, and ALT are important factors in evaluating the prognostic outcome of sepsis patients in the ICU. This suggests that medical professionals should recognize them expeditiously and implement aggressive treatment tactics to diminish the mortality rate and improve outcomes.