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Background White blood cell count is an important index to the outcome of patients. In hospital, leukopenia is accompanied by high mortality, morbidity and treatment costs. However, in infectious diseases, the reasons responsible for leucopenia was not well elucidated. We investigated patients with gastrointestinal fistula to find risk factors for leukopenia.Methods A prospective case control investigation was carried out in the Gastrointestinal Fistula Center, General Surgical Institute of Jinling Hospital. Cases included gastrointestinal fistula patients with leukopenia (n=98) and controls composed of gastrointestinal fistula patients with normal white blood cell count (n=78). The two groups were compared for risk factors of leucopenia by statistical analysis.Results Factors associated with an increased risk for leukopenia included bacterial infection (25.5%) and hypoalbuminaemia (61.2%). Multivariable Logistic regression analysis identified bacterial infection (80%), urinary catheter (70%) and central vein catheter (60%) as the independent determinants for mortality in cases.Conclusions In patients with gastrointestinal fistula, two independent factors for leukopenia and three significant predictors of mortality were elucidated. We suggest that clinicians give patients more supportive management and apply prevention strategies to treat and prevent leukopenia.