Suspected early onset sepsis drives most antibiotic use in the newborn nursery. The Kaiser Sepsis Calculator (KSC) is a validated tool that safely decreases laboratory evaluation and antibiotic administration in infants aged ≥34 weeks. Our quality improvement aim was a nurse-initiated, KSC-based program to decrease blood cultures (BCx) and complete blood counts (CBC) by 10% from March 2021 to October 2021 among chorioamnionitis-exposed infants born ≥35 weeks' gestation. A secondary aim was to decrease antibiotic administration by 10%. The KSC was implemented for infants at University Health, a county hospital affiliate of the University of Texas Health Science Center San Antonio, with a level I nursery and level IV NICU. The multidisciplinary project included pediatric hospitalists, neonatologists, family practitioners, maternal-fetal medicine physicians, fellows, residents, and nurses. All infants born 6 months before (August 2020-January 2021) and 7 months after protocol implementation (March 2021-September 2021) were analyzed. A total of 53 chorioamnionitis-exposed infants were included from the preintervention period and 51 from the postintervention period. CBC utilization decreased from 96% to 27%, BCx utilization decreased from 98% to 37%, and antibiotic utilization fell from 25% to 16%. In no cases were antibiotics prescribed against the KSC, and to our knowledge, no early onset sepsis diagnoses or infection-related hospital readmissions were missed. The multidisciplinary implementation of the KSC led to a reduction in testing, exceeding our initial goal. A nurse-initiated protocol reduced BCx, CBC, and antibiotic utilization among chorioamnionitis-exposed infants.