To determine the effect of implementation of an automated sepsis screening tool on the median cost of affected patient encounters. This retrospective cohort study used propensity score-matched comparison groups to assess the difference in median cost for comparable affected patient encounters before and after the implementation of an automated sepsis screening tool in a large US children's hospital emergency department (ED) with >90 000 annual visits. All patient encounters in 2018 impacted by the automated sepsis screening tool were included and compared with a propensity score-matched comparison group drawn from patient encounters in 2012 that might have been affected by the screening tool had it been active at that time. The main outcome was the change in the median cost for comparable affected patient encounters. The overall median cost for those affected by an automated sepsis screening tool decreased by 21.2%, from $6454 (IQR, $968-$21 697) to $5084 (IQR, $802-$16 618). The median cost for encounters with an associated International Classification of Diseases sepsis code decreased by 51.1%, from $58 685 (IQR, $32 224-$134 895) to $28 672 (IQR, $16 796-$60 657). The median cost for comparable patient encounters decreased with implementation of an automated sepsis screening tool in the pediatric ED. Costs were decreased even more substantially for patients with sepsis. In addition to improving outcomes, an automated sepsis screening tool appears to be at least cost-effective and may be cost-saving, an incentive for more widespread use of this technology.