Survival of elderly burn patients remains unacceptably poor despite modern and protocolized burn care. The acute phase, defined as the first 96 hours after burn, includes the resuscitation period and influences subsequent outcomes and survival. As the acute phase response of elderly burn patients is essentially unknown, the aim of this study was to determine if the acute phase post-injury is significantly different in elderly patients compared to adult burn patients. We included all patients admitted with an acute burn injury with a total body surface area (TBSA) ≥ 20% burn to our burn centre from 2010–2016. Clinical and laboratory measures during the acute phase, defined as 96 hours post-injury, were compared between adult (aged <65 years) and elderly (aged ≥65 years) patients. Outcomes included clinical hemodynamic measurements, biomarkers, volume of fluid resuscitation, cardiac agents, and the inflammatory response, determined in plasma by cytokine profiling. Data were analyzed using the Student’s t-test, Mann-Whitney U test, and Fisher’s exact test. A total of 149 patients were included, with 126 adults and 23 elderly. Inhalation injury and % TBSA burn were not significantly different among adult and elderly patients. Despite similar amounts and composition of resuscitation and fluid output, elderly had significantly lower heart rates (p<0.05), cardiac index (p<0.05), MAP (p<0.05), PaO2/FiO2 (p<0.05), and pH, along with higher lactate (p<0.05). Organ biomarkers, particularly creatinine and BUN showed distinct differences between adults and elderly (p<0.05). Elderly had significantly lower levels of IL-6, MCP-1, MCP-3, MIP-1α and MIP-1β during the acute phase (p<0.05). Elderly patients were hypometabolic relative to adult patients, with greater glucose and lipid variability (p<0.05). Overall mortality was significantly higher in elderly patients (5% vs. 52%, p<0.0001). Injury severity was similar between adult and elderly burn patients, but the response to the burn injury during the acute phase after injury is distinctly different. The acute phase in elderly is characterized by cardiac depression, hypoperfusion, and hypo-inflammation. The attenuated acute phase response in elderly burn patients might contribute to subsequent increased organ failure and mortality. While elderly might be predisposed to worse outcomes, further work on the cellular level is warranted to identify potential novel approaches to treat elderly burn patients.