In MVMR, assessing the genetic liabilities for PDW, PLC, and MPV jointly, PDW retained a robust relationship with 28-day mortality in sepsis, and the effect size of association was amplified with an OR of 1.23 (95% CI, 1.03–1.48; P < 0.05) using the IVW method. This evidence concerns the gene HSPG2 and Sepsis.