Kuppermann has been a federally-funded investigator[9][10][11] for many years and has particular interests in the clinical efficiency and utility of laboratory testing in the setting of the Pediatric Emergency Department.

[18] Kuppermann has extensive experience performing large, multicenter randomized controlled trials and observational studies pertaining to pediatric trauma.

He has served as a PI and Primary co-I on several extramural grants related to DKA and cerebral injury/edema in children, and one of his earliest research collaborations of the topic resulted in a highly-cited publication in the New England Journal of Medicine.

[3] This network is funded by HRSA/MCHB and EMSC and consists of 22 geographically and demographically diverse hospital pediatric emergency departments which evaluate ~ 1,300,000 children annually.

As a leader of PECARN, his work has helped shape the future concerning pediatric emergency care and advanced the ability to perform large-scale, multicenter research across the country.

Most currently, Kuppermann has investigated novel biomarkers and measured the host response to distinguish viral from bacterial infections in young febrile infants.