Burns are highly dynamic injuries characterized by an initial zone of necrosis that progresses to compromise surrounding tissue. Burn progression has profound clinical implications resulting in significant diagnostic and therapeutic challenges. Acute inflammation and cellular apoptosis are two of the main contributing factors in the burn progression. Higher morbidity and mortality, and poorer functional recovery are inevitable sequelae of burn progression. Connexin43 (Cx43), a building block of gap junctions, plays central modulating roles in both processes in traumatic injuries and chronic wounds. Cx43 antisense oligonucleotide was developed to downregulate Cx43 and accelerate chronic wound healing as therapeutics. Previously we showed a single dose of Cx43 antisense gel downregulates Cx43 protein expression in mouse burns leading to better healing and scarring. Immunofluorescence studies were carried out on human and rat burn tissues to establish the spatial and temporal correlation between Cx43, apoptosis and neutrophil response during the burn progression. Cx43-downregulating therapeutics were tested in a rat burn model to mitigate burn progression and improve healing and scaring. Our data shows a high level of Cx43 in human and rat burn wounds associated with activated neutrophils and apoptotic dermal cells. The Cx43-downregulation therapeutics mitigating burn progression should reduce the healthcare cost in burns care and allow better functional recovery of the burns patients.