The aim of the present study was to perform a comparative evaluation of TNF-α level in saliva and blood serum at children with severe disorders of the central nervous system (CNS) and conventionally healthy children in order to highlight the role of TNF-α in the initiation and development of dental caries. To assess the degree of the dental caries (DC) development were clinically examined 1272 children aged between 1 and 18 years. The study included 636 children with severe CNS disorders, which constituted the research group (L₁) and 636 conditionally healthy children formed the control group (L₀). The concentration of TNF-α in the oral fluid (OF) and blood serum was estimated in 212 children randomly selected from both groups. In children with severe CNS diseases TNF-α concentration in saliva is 5.53 times higher, and in blood serum it is 10.19 times higher compared to healthy children. In children with severe CNS diseases there was revealed a strong inverse relationship between TNF-α concentration in saliva and blood serum and the chances of avoiding new caries development, as opposed to the inverse average relationship estimated in healthy children. Excess TNF-α production, both locally and systemically influenced increased caries risk and dental caries morbidity in children with severe CNS diseases, which is necessary to consider when planning individualized prevention measures.