Purpose <p>To identify risk factors and characteristics associated with left ventricular diastolic dysfunction and investigate its correlation with mortality in sepsis patients.</p> Methods <p>A prospective cohort study was performed in sepsis patients between December 2022 and October 2023. Baseline characteristics, laboratory tests, treatments, echocardiographic results, and 28-day mortality were documented. Univariate and multivariate logistic regression analyses were conducted and a nomogram was constructed. Association between left ventricular diastolic dysfunction and 28-day mortality was analyzed.</p> Results <p>In total, 117 patients with a mean age of 58.3 ± 16.5&#xa0;years old and 63.3% men (74) were included. There were 75 (64.1%) and 42 (36.9%) patients with abnormal and normal diastolic dysfunction, respectively. Pneumonia, hematocrit, the ratio of E-wave peak velocity to A-wave peak velocity (E/A), ventricular septal early diastolic peak velocity of the mitral valve annulus (e′), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were associated with ventricular diastolic dysfunction (<i>P</i> &lt; 0.05). The nomogram constructed with these variables demonstrated high accuracy in predicting the occurrence of left ventricular diastolic dysfunction (area under the curve 0.938, sensitivity 83.8%, specificity 97.6%, Youden index 0.814). Left ventricular diastolic dysfunction could cause an increased 28-day mortality, with grade III diastolic dysfunction having the highest mortality rate (40.0%).</p> Conclusion <p>In sepsis patients, a nomogram based on pneumonia, hematocrit, E/A, ventricular septal e′, and NT-proBNP levels could accurately assess left ventricular diastolic dysfunction. Left ventricular diastolic dysfunction was associated with a high 28-day mortality, warranting further studies on the association between dysfunction severity and mortality risk.</p>