Objectives The systemic immune inflammation index (SII) is a novel biomarker based on platelet, neutrophil and lymphocyte counts. SII serum levels have diagnostic, prognostic degrees and correlations with various immune, inflammatory diseases. Celiac disease (CD) is an immune-mediated chronic enteropathy with inflammatory situations. Here we aimed to evaluate clinical significance of SII and to compare SII with other inflammatory markers in CD. Methods 161 pathologically confirmed CD and 75 dyspeptic patients were enrolled. Hemogram, biochemical markers, SII, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), mean platelet volume-to-platelet ratio (MPR) and monocyte-to-high density lipoprotein cholesterol ratio (MHR) were evaluated. Results There was a statistically significant difference between groups for SII (p<0.001). SII was statistically correlated with and superior to inflammatory markers in relation with CD. There were also statistically significant differences between groups for hsCRP, PLR, NLR, MPR, haemoglobin, platelet count, platelet volume distribution width, plateletcrit, ferritin, total cholesterol and HDL cholesterol (p=0.034; 0.015; 0.032; <0.001; <0.001; <0.001; 0.030; 0.001; <0.001; <0.001; 0.048, respectively). Correlations between SII and NLR, PLR, MHR, hsCRP were statistically significant (p≤0.001; <0.001; 0.033; 0.030, respectively). ROC analysis was used to determine the optimal cut-off value for CD by SII. A baseline SII level >560.0 was associated with CD with 64% specificity, 78% sensitivity (p<0.001). Conclusions To the best of our knowledge, this is the first study analyzed the diagnostic value of SII in CD. SII may serve as a beneficial marker for the diagnosis of inflammatory state superior to that of hsCRP, PLR, NLR, MHR, MPR and WBC.