In order to explore the effective markers of presepsis in the prediction of clinical disease and disease severity, the predictive effect of lactic acid (Lac) combined with cardiac troponin T (cTnT) and 5-hydroxytryptophan (5-HT) on the severity of sepsis in intensive care unit (ICU) patients and its correlation with prognosis is investigated. A total of 85 sepsis patients admitted to the ICU of our hospital from January 2020 to June 2021 are selected to establish the ICU sepsis group, and 72 health examination patients who received physical examination in our hospital during the same period are included in the healthy control group. The experimental results demonstrate that combined detection mode of serum Lac, cTnT, and 5-HT indicators has a high predictive value for the condition of patients with ICU sepsis and those indicators are closely correlated with the prognosis of patients. It suggests that the follow-up clinical monitoring of serum Lac, cTnT, and 5-HT indicators for patients with ICU sepsis can evaluate their condition and improve and optimize the clinical diagnosis and treatment plan effectively.