The aim . Microbiological monitoring of the digestive tract opportunistic microfl ora in underweight premature newborns to substantiate risk groups and the possibility of a personalized approach to manage such patients. Materials and methods . A case-control observational study included 67 preterm infants (35 boys and 32 girls), divided into three groups according to the underweight degree: low (n = 21), very low (n = 21) and extremely low (n = 25) mass. A comprehensive examination was carried out with clinical- anamnestic, laboratory and clinical- functional diagnostic methods, consultation of a neurologist, ophthalmologist, cardiologist. Microbiological monitoring of opportunistic microfl ora (UPM) of the oral cavity and other biotopes (auricle surface, armpit, fetal part of the placenta) was carried out on the 1st, 3rd and 7 th days of life. Biochemical identifi cation was carried out using test systems “Erba Lachema”. Database creation and statistical processing were carried out using software packages of Microsoft® Offi ce® 2010, IBM® SPSS® Statistics 23.0, WinPEPI© 11.39. Results . The frequency of opportunistic microfl ora isolated from the oral cavity of underweight newborns was signifi cantly higher on the 1st, 3rd days (Fisher’s exact test, p = 0.037) and was characterized by a wider spectrum compared to other studiedbiotopes. The dominant representative of opportunistic microfl ora in most biotopes was S. epidermidis , as well as K. pneumoniae , C. krusei , Burkholderia cepacia complex , and S. maltophilia . There was revealed a correlation link between the qualitative and quantitative parameters of opportunistic microfl ora, as well as the number of opportunistic microfl ora contaminated biotopes with the level of body weight and resistance indicators of underweight premature newborns. Conclusion . Microbiological monitoring of opportunistic microfl ora of the oral cavity and the inner surface of the auricle biotope makes it possible to consider these microecological parameters as a prognostic criterion for the course and outcomes in premature infants with underweight, as well as to scientifi cally substantiate a personalized approach to the management of such patients, the formation of risk groups, the appointment of corrective and preventive measures to form adequate profileof microbial colonization, prevent of infectious pathology and the decrease risk of an unfavorable outcome.