This study evaluated the effect of a combination of acetaminophen (AAP), vitamin C (VC) and thioctic acid (TA) on reducing serum cortisol concentrations in mice with foot-and-mouth disease (FMD) vaccination. For 5 days from 3 days before FMD vaccination to 2 days after vaccination, mice were orally administered with AAP 600 mg/kg feed (n=25, AAPT), combination of AAP 600 mg and VC 200 mg per kg feed (n=25, AVCT) and combination of AAP 600 mg, VC 200 mg and TA 20 mg per kg feed (n=25, AVTT), respectively. From day 1 to day 7 after FMD vaccination, the cortisol concentration of all groups treated with the drug was significantly decreased compared to that of the positive control group with FMD vaccination (p<0.05). In conclusion, the combined treatment of AAP, VC and TA was the most effective in relieving stress from FMD vaccination compared to the single treatment.