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Abstract Background Etomidate is an imidazole derivative that is widely used in the emergency department for Rapid Sequence Intubation (RSI). Although it has a safe hemodynamic profile, there are some concerns about its suppressant effects on the adreno-cortical axis. Vitamin C, as an antioxidant, can play a protective role in this issue. Method In a controlled clinical trial, we studied adult traumatic patients who needed RSI with etomidate. In one group underwent RSI with etomidate and cortisol levels were measured three hours later. In the other group, we administered one gram of vitamin C before etomidate administration, and the cortisol level was measured three hours later. Results Fifty-one patients have been studied. The serum cortisol level was significantly lower after RSI with etomidate in both groups. In the Vitamin C group, there was a significantly higher cortisol level after RSI in comparison to the control group. Conclusion Etomidate can suppress the cortisol level in trauma patients who undergo RSI. Vitamin C can reduce this suppressant effect of etomidate. Trial registration IRCT registration number: IRCT20090923002496N11, URL of trial registry record: https://en.irct.ir/trial/34586 , Date of trial registration: 19/04/2019. Full date of the first registration: 30/05/2019.