Background Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever and serosal inflammation. The aim of this study was to evaluate fecal calprotectin (FC) in children with FMF during the non-attack period. Methods A retrospective evaluation was made of the data of a total 66 patients diagnosed with FMF in an attack-free period and without amyloidosis or inflammatory bowel disease (IBD). FC level in the FMF patients was compared with that in the patients with IBD and healthy control subjects. Results The FMF patients consisted of 37 boys (56.1%) with a mean age of 10.1 +/- 3.9 years. Mean FC was 192.5 mu g/g (range, 19.5-800 mu g/g) in the FMF group, 597.9 mu g/g (range, 180-800 mu g/g) in the IBD group, and 43.8 mu g/g (range, 19.5-144 mu g/g) in the control group. The FC level in the children with FMF was higher than in the control group (P < 0.001), and the FC level of the IBD patients was higher than both the FMF and the control groups (P = 0.020, P < 0.001, respectively). Conclusions FC was higher in FMF patients compared with healthy children even in the absence of IBD/amyloidosis. Even though colonoscopy is the gold standard in identifying intestinal inflammation in FMF patients, FC, a non-invasive and inexpensive method, can be used for screening. The presence of subclinical intestinal inflammation was also quantitatively identified in children with FMF.