The objective of this study was to assess the energy demand and economic cost of two hospital-based COVID-19 infection control interventions. The intervention control measures evaluated include use of negative pressure (NP) treatment rooms and xenon pulsed ultraviolet (XP-UV) infection control equipment. After projecting COVID-19 hospitalizations, a Hospital Energy Model and Infection De-escalation Models are applied to quantify increases in energy demand and reductions in secondary infections. The scope of the interventions consisted of implementing NP in 11, 22, and 44 rooms (at small, medium, and large hospitals) while the XP-UV equipment was used eight, nine, and ten hours a day, respectively. The annum kilowatt-hours (kWh) for NP (and costs were at $0.1015 per kWh) were 116,700 ($11,845), 332,530 ($33,752), 795,675 ($80,761) for small, medium, and large hospitals ($1,077, $1,534, $1,836 added annum energy cost per NP room). For XP-UV, the annum kilowatt-hours and costs were 438 ($45), 493 ($50), 548 ($56) for small, medium, and large hospitals. There are other initial costs associated with the purchase and installation of the equipment, with XP-UV having a higher initial cost. 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.