The study investigated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on burn-induced coagulopathy in severely burned patients. Patients with a greater than 20% TBSA were identified in the TriNetX research network and categorized into receiving or not receiving NSAIDs in the first week after the burn. The statistical significance of the rate of burn-induced coagulopathy, mortality and sepsis in the week following injury was analysed. We observed 837 severely burned patients taking NSAIDS during the week following the burn and 1036 patients without. After matching for age, gender and race, the risk of burn-induced coagulopathy significantly decreased (p < 0.0001) in patients taking NSAIDs (17.7%) compared to those without (32.3%). Patients taking NSAIDs were also less likely to develop sepsis (p < 0.01) and thrombocytopenia (p < 0.001) or die the week following injury (p < 0.0001). In conclusion, the early protective effects of NSAIDs at reducing the risk of coagulopathy as well as sepsis and mortality occur during the acute phase of burns.