Introduction: The mal-absorption and the inflammation participate in the pathogenesis of Crohn__ampersandsignrsquo;s disease (CD) and influence the vitamin D levels. Serum microRNAs (miRNAs) are secreted during the inflammation in the gastrointestinal tract and therefore could affect the regulatory functions of vitamin D and its signal pathways via negative feedback. Objective: This study aims to assess the relationship between the Vitamin D serum levels and the expression of several circulating miRNAs in patients with CD and to correlate their levels with the activity of the disease. Methods: 15 miRNAs expression was assessed using reverse transcriptase quantitive real-time PCR in 27 consecutive CD patients and then correlated with the serum level of 25(OH)D, C-reactive protein (CRP), faecal calprotectin (FCP) and clinical Crohn__ampersandsignrsquo;s disease assessment index (CDAI). Results: Activity of CD is a risk factor for a decrease in the 25(OH)D serum levels (OR=7.5 (1, 09-51, 52; p__ampersandsignlt;0.05). There is a strong inverse correlation between the levels of FCP and 25(OH)D (r=-0.641; p__ampersandsignlt;0.001). The results indicate that 25(OH)D deficiency induces the highest risk for a change in the miRNA-96_1 serum expression. Conclusion: The 25(OH)D serum levels and serum expression of miRNA-96_1, miRNA-142-5?_1, miRNA-191_1 and miRNA199?_1 open an opportunity for optimization of the initial assessment of CD and potential as a prognostic tool.