BACKGROUND: The advantages of laparoscopic surgery have been well documented. However, the impact of pneumoperitoneum on sepsis sequelae is still equivocal. This study aimed to evaluate the effect of CO(2) pneumoperitoneum, applied under different pressures and exposure times, on sepsis cascade and mortality.MATERIAL AND METHODS: In 42 New Zealand rabbits, peritonitis was induced by the cecum ligation and puncture model. After 12 h, the animals were randomized in seven groups: a control group, four groups with pneumoperitoneum (10-15 mmHg for 60-180 min), and two groups with laparotomy (for 60 and 180 min). Blood samples were collected before cecum ligation and puncture, 12 h later and 1, 3, and 6 h after pneumoperitoneum desufflation or abdominal trauma closure to evaluate bacteremia, endotoxemia, white blood cells count, C-reactive protein, and procalcitonin levels. Furthermore, the mortality time was recorded in all animals.RESULTS: Bacteremia and endotoxemia were induced in all groups. Endotoxemia levels were significantly more elevated in the group where pneumoperitoneum was performed under 15 mmHg for 180 min compared with all other groups at 1 and 3 h after pneumoperitoneum desufflation (P < 0.05), except when compared with the group where pneumoperitoneum was performed under 10 mmHg for 180 min. White blood cell and C-reactive protein levels showed similar trends for all groups. However, serum procalcitonin reached statistically higher levels (P < 0.05) in groups with laparotomy compared with groups with pneumoperitoneum and with the control group at 6 h. Survival was lower in the laparotomy groups compared with the pneumoperitoneum groups and with the control group (P < 0.05).CONCLUSIONS: In the presence of peritonitis, CO(2) pneumoperitoneum applied in clinically standard pressures, even for extended time intervals, reduces the severity of sepsis and prolongs survival.