Some patients with perianal infection fall into a critical condition with severe sepsis and septic shock (lethal perianal infection). The objective of this study is to clarify the clinicopathological characteristics of, and treatment strategies for, lethal perianal infection. The clinical records of 7 patients with lethal perianal infection were examined. For two rapidly dying cases (within 3 days), we performed resection of the rectum or local anal drainage as a primary management of damage control. These patients were transferred to our center because of septic shock and multiple organ dysfunction syndrome (MODS) and had received insufficient fluid resuscitation in the previous hospital. Another nonsurviving case who died on the 16th day was transferred without MODS and underwent perianal drainage but could not recover from shock, even after repeated surgical procedures were performed. To prevent a perianal infection from becoming lethal, it should be managed as early as possible with sufficient fluid resuscitation with adequate drainage.