Spontaneous bacterial peritonitis (SBP) is associated with an important production of inflammatory mediators. However, it is unknown whether there is a relationship between the abdominal production of these mediators and the development of renal impairment, one of the most important prognostic parameters in spontaneous bacterial peritonitis. We studied 52 cirrhotic patients at diagnosis and resolution of the infection, by measuring endotoxin, tumor necrosis factor (TNF), and interleukin-6 (IL-6) levels in plasma and ascitic fluid. Thirteen patients (25%) developed renal impairment. Patients developing renal impairment showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection than patients who did not (plasma TNF-α: 96.0 ± 38.7 vs. 39.1 ± 3.6 pg/mL, P = .0209; ascitic fluid TNF-α: 474.5 ± 118.1 vs. 160.8 ± 42.7 pg/mL, P = .0173; plasma IL-6: 6,635 ± 2,897 vs. 458 ± 109 pg/mL, P = .0004; ascitic fluid IL-6: 182,559 ± 47,328 vs. 39,250 ± 10,803 pg/mL, P = .0001). Independent predictors of development of renal impairment at diagnosis were: renal failure (blood urea nitrogen > 30 mg/dL or serum creatinine > 1.5 mg/dL) (P < .001), IL-6 levels in ascitic fluid (P < .001), and mean arterial pressure (P < .05). Ten of the 13 (77%) patients who developed renal impairment died during hospitalization, but only 2 of the 39 (5%) patients who did not (P= .0001). In addition, renal failure at diagnosis of the infection was the only independent predictor of hospital mortality (P < .001). In conclusion, the inflammatory response to the infection may be an important mechanism of renal impairment and the associated mortality in SBP.