ABSTRACT: The study objective assessed the energy demand and economic cost of two hospital-based COVID-19 infection control interventions: negative pressure (NP) treatment rooms and xenon pulsed ultraviolet (XP-UV) equipment. After projecting COVID-19 hospitalizations, a Hospital Energy Model and Infection De-escalation Models quantified increases in energy demand and reductions in infections. The NP intervention was applied to 11, 22, and 44 rooms for small, medium, and large hospitals, while the XP-UV equipment was used eight, nine, and ten hours a day. For small, medium, and large hospitals, the annum kWh for NP rooms were 116,700 kWh, 332,530 kWh, 795,675 kWh, which correspond to annum energy costs of $11,845 ($1,077/room), $33,752 ($1,534/room), and $80,761 ($1,836/room). For XP-UV, the annum-kilowatt-hours (and costs) were 438 ($45), 493 ($50), and 548 ($56) for small, medium, and large hospitals. While energy efficiencies may be expected for the large hospital, the hospital contained more energy-intensive use rooms (ICUs) which resulted in higher operational and energy costs. XP-UV had a greater reduction in secondary COVID-19 infections in large and medium hospitals. NP rooms had a greater reduction in secondary SARS-CoV-2 transmission in small hospitals. Early implementation of interventions can result in realized cost savings through reduced hospital-acquired infections.