Mouse survival was affected by the severity of cecal ligation and puncture (CLP), and the timing of systemic interferon (IFN) β administration. Kaplan-Meier analysis of mice subjected to mild sepsis (cohort 1, n = 11), severe sepsis control (cohort 2, n = 48), severe sepsis and therapeutic IFNβ (cohort 3, n = 34), and severe sepsis with prophylactic IFNβ (cohort 4, n = 24). On day 6, survival in cohort 2 (25%) was significantly lower than in cohort 1 (81.8%; log-rank test, P = 0.002). Compared with cohort 2, the survival of therapeutic IFNβ-treated mice (cohort 3) was significantly improved (52.9%; log-rank test, P = 0.017). In contrast, prophylactic IFNβ-treated mice (cohort 4) had significantly lower survival rates than severe sepsis controls (4.1%; log-rank test, P = 0.001). Data represent combined results from six separate survival experiments, each with similar results. ATB = antibiotics.