Postoperative sepsis is the leading cause of morbidity and mortality after major surgery, resulting in hefty financial costs in hospitals all over the world. 40 Fischer rats were injected intra-peritoneally with 0.05 ml Covexin 10 which contains toxoids from different Clostridial species, 2 weeks prior to caecal ligation and puncture. Another 40 Fischer rats, as a control, underwent caecal ligation and puncture without vaccination. 16 of 40 vaccinated rats died (40%), peritoneal fluid cultures from the dead rats grew E. coli only, and 36 of 40 control rats died (90%), peritoneal fluid cultures from the dead rats were: 19 grew E. coli and C. perfringens; 12 grew E. coli,C. perfringens, and enterococci; 3 grew E. coli only; 1 grew E. coli, and enterocci; and 1 grew no organisms. Prophylactic vaccination with clostridial toxoids proved effectiveness in preventing anaerobic infection, and reduce mortality in rats that underwent caecal ligation and puncture; the gold standard model for polymicrobial sepsis. Currently, a pilot study is underway in which human patients who will undergo major surgery are prophylactically vaccinated with clostridial toxoids, in an attempt to eradicate postoperative anaerobic sepsis.