In the neonatal intensive care unit（NICU），maternal separation（MS）and pain are identified as two of the most prevalent early stressors experienced by infants.These stressors have been demonstrated to result in a range of adverse effects on the developing infant，including but not limited to increased pain sensitivity，alterations in neuroplasticity，dysregulation of the endocrine system，immune response imbalance，as well as the emergence of anxiety and depression.To further elucidate their potential mechanisms，this paper presents a summary of recent animal models investigating neonatal MS and pain，while also reviews advancements in understanding how these early stressors impact organisms and their underlying mechanisms.The objective is to provide novel insights and scientific evidence with a view to prevent potential adverse outcomes for infants in the context of hospitalisation in the NICU.