To investigate the efficacy and safety of Chinese herbal medicine in treating sepsis patients with bloodstream infection.A 6-year retrospective study was carried out at a university hospital in China. Adult sepsis patients with bloodstream infection were included. The primary outcome was 28-day mortality after admission. Propensity score method was used to adjust for possible confounding. 28-day mortality was estimated by Kaplan-Meier analysis and compared using the log-rank test. Cox regression analysis was carried out to identify factors impacting in-hospital mortality outcomes.Following the application of the propensity score method, a total of 176 patients were included. The all-cause 28-day mortality in the control group and Chinese herbal medicine group was 21.6% and 14.8%, respectively. Kaplan-Meier survival analysis showed that Chinese herbal medicine was associated with a lower hazard ratio (HR) in all-cause 28-day death compared with the control group [HR = 0.44, 95% CI(0.22, 0.90), P < 0.05]. The complications were similar between the two groups (P >0.05). Blood-activating and stasis-eliminating herb administration was associated with reduced in-hospital mortality among sepsis patients with bloodstream infection [HR = 0.54, 95% CI(0.34, 0.94), P < 0.05].Chinese herbal medicine, especially the blood-activating and stasis-eliminating herb, might have certain efficacy and safety in treating sepsis patients with bloodstream infection. Clinicians should prescribe blood-activating and stasis-eliminating herb in treating these two coalescent critical diseases as long as no contraindications exist. However, further studies are needed to validate our results.