Preterm infants, due to immature and dysfunctional skin, have increased water loss through the skin and consequently a decreased body temperature. In order to develop protective garments for preterm infants, it is important to select materials that will protect the child against water and heat loss. The authors are currently involved in the development of protective garments for premature babies, which are similar to baby clothes and contain a membrane that is partially permeable for vapor in combination with textile materials. This article presents the study of materials intended for the production of protective garments for pre-term infants. Samples of materials were investigated to determine biophysical comfort (tests of heat resistance, vapor resistance according to PN-EN ISO 11092:2014-11 and air permeability according to PN-EN ISO 9237) and porosity, surface mass in accordance with PN-EN 12127, and thickness in accordance with PN-EN ISO 5084. In order to determine the porosity of materials and to visualize the structure, tests on computer microtomography were carried out. The mechanical properties of the tested materials and the evaluation of the total hand value were characterized; the samples were tested on the KES device. The aim of this study was to select the most suitable fabrics for protective garments for premature infants to prevent excessive heat and moisture loss from the body, which can lead to hypothermia. For laminates, the optimal results of vapor resistance and heat resistance were obtained for laminate (15 g·m−2 PE foil + 15 g·m−2 PP non-woven), with a level of thermal resistance of 0.0766 m2·K·W−1 and vapor resistance of 188.729 m2·Pa·W−1, and for laminate (15 g·m−2 PE foil + 10 g·m−2 PP non-woven), with a level of thermal resistance of 0.0683 m2·K·W−1 and vapor resistance of 164.085 m2·Pa·W−1. For knitted fabrics, knitwear single cotton 155 g·m−2 showed the highest thermal resistance (0.0296 m2·K·W−1), and knitwear interlock polyester 120 g·m−2 showed the lowest thermal resistance (0.0179 m2·K·W−1). Knitwear cotton 120 g·m−2 had the highest water vapor resistance (8.402 m2·Pa·W−1), while knitwear interlock polyester 130 g·m−2 sample had the lowest resistance (6.356 m2·Pa·W−1). Garments for premature babies should have moisture barrier properties and high thermal insulation. They should also be characterized by optimal air permeability properties. Sample two-layer laminate (15 g·m−2 PE foil + 15 g·m−2 PP non-woven) had the best vapor resistance and thermal insulation properties. Moreover, this sample was characterized by good air permeability and surface weight compared to the other laminate samples. During the design of garments for premature babies, it is important to reduce the surface weight to as low as possible. Among the knitted fabrics, a knitwear single cotton 120 g·m−2 knitwear polyester interlock 120 g·m−2 was selected for having the best THV or tactile comfort. In addition, these knits were chosen for their lower surface weight. Based on the conducted tests, two-layer laminate (15 g·m−2 PE foil + 15 g·m−2 PP non-woven), the knitwear single cotton 120 g·m−2, and knitwear polyester interlock 120 g·m−2 were selected for further research. [ABSTRACT FROM AUTHOR]