BACKGROUND Serum lactate, troponin, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been proposed to be useful prognostic indicators in patients with sepsis and septic shock. This study aimed to evaluate the predictive ability of these biomarkers and assess how their prognostic utility may be improved by using them in combination. MATERIAL AND METHODS A retrospective review of the medical records of 1242 patients with sepsis and septic shock who were admitted to the Richmond University Medical Center between June 1, 2018, and June 1, 2019, was carried out; 427 patients met the study criteria and were included in the study. The primary outcome measures included 30-day mortality, APACHE II scores, length of hospital stay, and admission to the Medical Intensive Care Unit (MICU). RESULTS High levels of lactate (>4 mmol/L), troponin (>0.45 ng/mL), and NT-proBNP (>8000 pg/mL) were independent predictors of 30-day mortality, with an adjusted odds ratio of mortality being 3.19 times, 2.13 times, and 2.5 times higher, respectively, compared with corresponding reference groups, at 95% confidence intervals. Elevated levels of lactate, troponin, and NT-proBNP were associated with 9.12 points, 7.70 points, and 8.88 points in higher APACHE II scores, respectively. Only elevated troponin levels were predictive of a longer length of hospital stay. In contrast, elevated lactate and troponin were associated with an increased chance of admission to the MICU. CONCLUSIONS Elevated levels of serum lactate, troponin, and NT-proBNP are independent predictors of mortality and higher APACHE II scores in patients with sepsis and septic shock.