Within the United States, 500,000+ individuals are enduring the long-term consequences of severe burn injuries covering 20% or more of their body surface area, with upwards to 11,000 individuals experiencing such an injury per year. These burn injuries severely compromise body temperature regulation, owing to permanent impairments of the primary heat-dissipating mechanisms, namely profoundly blunted skin blood flow and sweating in the injured skin. Furthermore, well-healed burn survivors exhibit greater all-cause mortality; more hospitalization days for “circulatory diseases” including heart disease, heart failure, and cerebrovascular disease; and have elevated incidences of diabetes, hypertension, coronary artery disease, and stroke. For more than 20 years, the PI has investigated the adverse consequences of severe burn injuries while focusing on two primary goals: a) providing important information to the burn survivor and their caregivers, targeted at improving the quality of life for burn survivors, and b) provide research-verified findings directed at reducing the elevated morbidity and mortality risk in well-healed burn survivors. Consistent with those goals, the objective of this MIRA application is to extend our discoveries, and associated understanding, of the cardiovascular and thermoregulatory consequences of a severe burn injury in humans and to pursue avenues to mitigate any such adverse consequences. Though specific aims are not permitted in MIRA applications, examples of research directions that could be pursued include quantifying cardiovascular function/dysfunction very early after a severe burn injury (e.g., within the first ~48 hours post-burn), at discharge from the hospital post-burn, and months after discharge; assessments of cardiac and renal stress due to physical activity in warm to hot environmental conditions in well-healed burn survivors while exploring avenues to mitigate any adverse responses; and perhaps identify the limits that a severe burn injury places on well-healed burn survivors’ thermoregulatory and cardiovascular capabilities to withstand adverse conditions associated with heat waves while also exploring approaches to mitigate such adverse responses. These research efforts will provide valuable information that will culminate in the reduction in otherwise heightened morbidity and mortality burden of burn survivors, along with associated improvements in cardiometabolic health, a greater ability to work and perform functions of daily living, improved quality of life, and enhanced independence as they age.