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Background: Although routine nurse caregiving is vital for the overall health of preterm infants, variations in approaches may exert distinct effects on preterm infants' stress responses and behavior state., Purpose: The purpose of this systematic review was to examine routine nurse caregiving in the neonatal intensive care unit and its effect on stress responses and behavior state in preterm infants., Data Sources: A systematic search was conducted using PubMed, Embase, and CINAHL for studies published between 2013 and 2023., Study Selection: Included studies enrolled preterm infants born <37 weeks gestational age and investigated nurse caregiving practices and effects on stress responses and/or behavior state., Data Extraction: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, data about study design, methods, findings, and limitations were extracted and summarized. Included studies were evaluated for bias using the National Health, Lung, and Blood Institute quality assessment tools., Results: All 13 studies included in the review received a fair quality rating. Nurse caregiving activities, including suctioning, diaper changes, bathing, and weighing, were associated with increases in heart and respiratory rates, blood pressure, energy expenditure, and motor responses, lower oxygen saturations, and fewer sleep states., Implications for Practice and Research: Adapting nurse caregiving frequency and duration, aligning caregiving with infant state, and integrating developmental care strategies may reduce infant stress responses and support behavioral rest. Further research is needed to understand how caregiving activities affect stress responses and behavior state in preterm infants, aiding in identifying modifiable caregiving stressors to promote optimal development., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 by The National Association of Neonatal Nurses.)