Background: Plasma is commonly used in patients with coagulopathy; however, its role in patients with sepsis-induced coagulopathy (SIC) is unclear. This study aimed to evaluate the effect of plasma transfusion on the prognosis of patients with SIC. Methods: Data were collected from the Medical Information Mart for Intensive Care IV database. Multivariable logistic regression analysis was used to determine the association between plasma transfusion and the incidence of in-hospital mortality, pulmonary embolism, and lower extremity deep vein thrombosis in critically ill patients with SIC. Propensity score matching (PSM) and propensity score–based inverse probability of treatment weighting (IPTW) models were used to ensure the robustness of our findings. Furthermore, the nonparametric relationship between in-hospital mortality and plasma transfusion volume was analyzed using restricted cubic spline. Subgroups analyses were performed for age, sex, Charlson score, Sequential Organ Failure Assessment score, SIC score, and with hemorrhage. Results: A total of 8,747 patients with SIC were enrolled: of them, 1874 were in the plasma infusion group, and 6,873 were in the no plasma infusion group. Compared with the no plasma infusion group, the plasma infusion group had higher in-hospital mortality (odds ratio [OR], 1.4411; 95% confidence interval [CI], 1.2280–1.6897, P < 0.05), and the results were robust after PSM (OR, 1.3227; 95% CI, 1.1152–1.5697; P < 0.05) and IPTW (OR, 1.1541; 95% CI, 1.0738–1.2404; P < 0.05). Similar results were also observed in different subgroups. However, because of conflicting results after PSM and IPTW, we were unable to definitively link plasma transfusion with pulmonary embolism and deep vein thrombosis. Compared with the no early plasma transfusion group (≥12 h), the in-hospital mortality rate was lower in the early plasma transfusion group (<12 h) (OR, 0.5426; 95% CI, 0.4398–0.6844; P < 0.05). The restricted cubic spline analysis indicated that increased plasma transfusion was associated with increased in-hospital mortality in patients with SIC. Conclusion: Plasma transfusion increases in-hospital mortality in patients with SIC, and the mortality rate increases with the amount of plasma transfusion. Patients with SIC who received early plasma infusion had lower in-hospital mortality than those who received no early plasma transfusion.