INTRODUCTION: Discomfort, pain, and stress have an adverse impact on the psychomotor development in the premature newborn infant. Recent studies indicate that pain and stress are associated with a reduction of parasympathetic outflow. We hypothesized that cocooning associated with the human voice has a favorable impact on parasympathetic activity in the premature newborn infant. METHOD: We compared heart rate variability (HRV) before and after standardized cocooning phases associated with the human voice and carried out: 1) by the mother and 2) by a third person. HRV was assessed and expressed as an index reflecting the parasympathetic tone. RESULTS: Ten children were included (median gestational age, 33 weeks (30(+4)-33(+2))). We observed a higher HRV index after the period of cocooning associated with the human voice compared with the baseline measurement (P<0.05), whether the procedure was carried out by the mother or a third person. CONCLUSION: This study shows that cocooning associated with the human voice enhances HRV in the preterm newborn infant, indicating an increase in parasympathetic activity after cocooning associated with the human voice. However, the impact is similar whether the cocooning associated with the human voice is performed by the mother or a third person. This result suggests that cocooning associated with the human voice carried out either by the mother or a third person contributes to decreasing stress and discomfort in the premature newborn infant.