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The aim of this study was to explore the association of an elevated modified shock index (MSI) in sepsis and myocardial dysfunction.This single center exploratory retrospective cohort study was conducted at Mayo Clinic from 2011 to 2014. It includes adults admitted to the medical intensive care unit with severe sepsis or septic shock. The time MSI > 1.3, area under the curve, in the first 6 h was assessed using logistic regression for primary outcomes of myocardial dysfunction and depression and secondary outcomes including mortality and SOFA score.Overall 578 individuals met inclusion criteria, 169 (29%) developed myocardial dysfunction and 23 (4%) myocardial depression. Adjusted for age, gender, Charlson score, and baseline APACHE 3 score, area MSI > 1.3 was associated with increased odds of myocardial dysfunction (OR 1.10, 95% CI 1.00–1.21; p = 0.058) and depression (OR 1.28, 95% CI 1.07–1.53; p = 0.007). Associations were also seen with ICU mortality (OR 1.17, 95% CI 1.04–1.32; p = 0.011), hospital mortality (OR 1.13, 95% CI 1.02–1.25; p = 0.025) and SOFA score.Elevated modified shock index during early sepsis is associated with the development of myocardial dysfunction and depression, SOFA score and mortality.Identify myocardial dysfunction in sepsis to provide supportMSI is a bedside calculation of HR/MAP.Elevated MSI is associated with myocardial dysfunction, mortality and organ failure.