Our objective was to investigate the effect of continuous therapeutic sedation on the immune response, plasma levels of antioxidants, and tissue repair indicators in burn-induced sepsis patients. A total of 104 burn-induced sepsis patients hospitalized during March, 2008 to March, 2013 were selected for the study and randomly divided into the experimental and control groups, each with 53 cases. All of these patients received conventional treatment and the patients in the experimental group were given an additional therapy of continuous sedation. The number of T lymphocytes, plasma levels of tissue repair indicators, and antioxidants were measured before and after the treatment. Continuous midazolam treatment induced a significant increase in plasma levels of gelsolin, heat shock protein 70, nitric oxide, superoxide dismutase, and tumor necrosis factor-alpha (p < 0.05). Likewise, the relative counts of CD3+, CD4+, CD8+ T lymphocytes, T cells exhibiting HLA-DR and CD4+/CD8+ ratio were significantly increased in the patients treated with midazolam. No adverse reaction including respiratory depression, midazolam resistance, or withdrawal syndrome was observed. Continuous sedation therapy was found to enhance immune response, increase the plasma levels of antioxidants, and tissue protective/repair mediators in burn-induced sepsis patients. This therapy caused no adverse reaction or over-inhibition of the oxidative stress suggesting its effectiveness in improving the prognosis without the risk of safety.