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Calprotectin is a marker associated with intestinal inflammation. The aim of this study is to explore the diagnostic value of fecal calprotectin in predicting bacterial/viral diarrhea and the application of fecal calprotectin in the clinical course of infectious diarrhea.Patients ages from 3 months to 10 years with infectious diarrhea were enrolled, and from each patient, 2 to 3 stool samples were collected. Fecal calprotectin levels were determined by enzyme-linked immunosorbent assay and compared by pathogen and disease activity. A univariate linear regression was used to determine the correlation between fecal calprotectin and the clinical parameters, and generalized estimating equations (GEEs) were used for the time course analyses.The data include 451 evaluations for 153 individuals across 3 different time points. The fecal calprotectin level was higher in patients with Salmonella infection (median with range 765 [252–1246] μg/g) or Campylobacter infection (689 [307–1046] μg/g) compared with patients with rotavirus infection (89 [11–426] μg/g), norovirus infection (93 [25–405] μg/g), or adenovirus infection (95 [65–224] μg/g). Fecal calprotectin concentrations were elevated in patients with severe (843 [284–1246] μg/g) or moderate (402 [71–995] μg/g) disease activity compared with those with mild (87 [11–438] μg/g) disease activity (P < 0.05). GEE analysis suggests that fecal calprotectin is correlated with clinical severity (eg, Vesikari score) and may provide information for disease management.Fecal calprotectin levels increased during bacterial infection and as disease severity increased, and its levels on the initial evaluation and follow-up visit are correlated with clinical severity. Fecal calprotectin may be a useful marker for application in children during infectious diarrhea.