Sepsis is still a major cause of the high mortality rate in the intensive care unit. Many studies have been published about the severity of sepsis, but the cause of mortality in sepsis and multiorgan failure is still obscure. This study investigated the effects of caffeic acid phenethyl ester (CAPE) particularly on the inflammatory and related histopathological changes in the lung, liver and kidney in an experimental sepsis model. Forty Sprague Dawley rats were used in this study, and were divided into four groups of ten rats each, as follows: Group I was given intraperitoneal saline infusion treatment. Group II was given intraperitoneal CAPE infusion treatment. Sepsis was induced in the animals in Group III (sepsis with saline infusion), while Group IV rats underwent induced sepsis plus CAPE infusion treatment (sepsis with CAPE infusion). Sampling was performed 48 h after treatment. The induction of sepsis resulted in a significant increase in serum glucose, leukocytes, urea, creatinine, LDH levels in BAL, plasma MDA, AST and ALT levels in the sepsis + saline group. The use of CAPE significantly decreased these parameters. Histopathological examination revealed less congestion, portal inflammation, and focal necrosis of the liver, and less congestion, edema, and emphysematous and inflammatory changes in the lung in the sepsis + CAPE group than in the other groups. These results support that CAPE may be used for the treatment of organ failure during sepsis.