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Objective: The aim of the sthudy is to sthudy the level of soluble Immune Checkpoint Molecules (B7.2, CTLA-4, Tim-3, Lag-3, PD-1) in the oral fluid during dental caries with the background of a lack and/or deficiency of 25-hydroxy-vitamin D in body., Materials and Methods: During the research 3 groups of people were formed, each one of them included 17 people aged from 20 to 24 years. The first group included students with high-intensity caries (above 9 DMFt index) and 25-hydroxy-vitamin D levels in blood serum >30 ng/ml, the second included students with high caries intensity and 25-hydroxy-vitamin D levels <30 ng/ml. The control group consisted of students with an average DMFt index of 1.5 (from 0 to 3) and a level of 25(OH)D in the blood more than 30 ng/ml. To determine the content of B7.2 (CD86), CTLA-4, Tim-3, Lag-3, PD-1, the Human Vascular Inflammation Panel 1 multiplex analysis kit from Biolegend (USA) was used., Results: The results of the research showed that during dental caries with a normal level of 25-hydroxy-vitamin D there are no significant changes in the content of Immune Checkpoint Molecules. With the background of deficiency and lack of 25-hydroxy-vitamin D there is a decrease in the amount of B7.2, LAG-3, Tim-3 and PD-1. These changes are being aggravated with an increase of the caries intensity., Conclusion: Vitamin D deficiency leads to a decrease in mucosal immunity of the oral cavity, the multiplication of pathogenic microorganisms, which in turn, releasing various metabolites, including cytokine-like substances, aggravate the pathological process and intensify carious lesions.