Abstract: This study was carried out to evaluate the possible protective role of some serum factors like pH and adequate level of calcium, phosphate and fluoride in dental caries. A total of 100 subjects of either sex, aged 10-40 were selected. Decayed, Missed and Filled Teeth (DMFT) were used as indices for scoring the dental caries and were distributed into 4 groups on the basis of DMFT indices as 4-8 (Group I), 9-16 (Group II), 17-24 (Group III) and more than 25 (Group IV), while the control subjects had DMFT index equal to or less than 3. Serum was collected and pH, calcium, phosphate, fluoride and lactic acid were analyzed. Patients of dental caries showed significantly decreased levels of calcium, phosphate, fluoride (p<0.001) and significantly increased level of lactic acid (p<0.001) were observed in Groups I, II, III and IV as compared to controls. Among groups prominent significant changes were observed in Group IV. This study did not show any significant change in serum pH with the progression of disease. From the findings of present study, it can be concluded that the adequate level of calcium, phosphate and fluoride is responsible for the significant deposition of these minerals in plaque which greatly reduces the developmental caries in the adjacent enamel.