Introduction: The wrapping of the newborn in an orthopedic tubular mesh, simulating a cocoon, can allow the infant to regain the feeling of security and stability experienced in the uterus given that the movement of one of the parts of the body exerts tactile and pressure variation in others. Objective: We aimed to evaluate the influence of an orthopedic tubular mesh, simulating a cocoon, in therapeutic positioning, on the variables of the autonomous, motor, and regulatory systems of preterm newborns. Methods: A controlled and randomized clinical trial was conducted with preterm newborns positioned in dorsal decubitus and divided into two groups: (a) cocoon – newborns covered with an orthopedic tubular mesh, and (b) control – newborns positioned according to the sector's routine and without the use of an orthopedic mesh. During the follow-up, each newborn was placed in the position for 30 min and was recorded for a total of 2 min, once at the beginning and again at the end of the observation period. Variables related to the autonomous system (heart rate, respiratory rate, and peripheral oxygen saturation), motor system (general movements), and regulatory system (Neonatal Infant Pain Scale) were evaluated before and after the intervention. The videos were evaluated by a researcher blind to the purpose of the study, and the resulting data were analyzed using SPSS. Results: Of the 40 preterm newborns evaluated (32.5 ± 1.83 weeks), 21 were female, and 20 were allocated to the cocoon group. The variables related to the autonomous, motor, and regulatory systems remained unchanged following the positioning in the cocoon, as compared to the typical positioning employed in the neonatal unit. Conclusion: The simulation of a cocoon, utilizing an orthopedic tubular mesh, when applied to preterm newborns admitted to a neonatal intensive care unit can contribute to maintaining low levels of stress, without altering variables of the autonomous, motor, and regulatory systems.