Background. Obstructive jaundice (OJ) predisposes patients to postoperative sepsis. We determined whether OJ led to an increased endotoxin stimulated tumor necrosis factor-α (TNF-α) production by macrophage-rich organs and whether a lack of intraluminal gut bile contributed to this increased sensitivity. Methods. Rats underwent laparotomy and common bile duct ligation and division (CBDL) or sham operation after they were given low-dose endotoxin or saline solution (NS). TNF-α levels in plasma, perfusate from the isolated perfused rat liver, and tissue from lung, spleen, and liver were measured 90 minutes later. An additional group underwent creation of a choledochal-vesical fistula and endotoxin administration. Results. The plasma TNF-α, liver perfusate TNF-α, and the tissue TNF-α levels in liver, lung, and spleen were significantly elevated in the CBDL + endotoxin (CBDL + ETX) group compared with the SHAM + ETX and CBDL + NS groups (p < 0.05). The choledochal-vesical fistula group after endotoxin had plasma TNF-α levels only 27% that of the CBDL + ETX group (p < 0.05). Conclusions. OJ sensitizes macrophage-rich organs to produce larger amounts of TNF-α in response to endotoxin. This sensitization is not solely due to decreased intraluminal gut bile.