Staphylococcus aureus is a Gram-positive bacterium causing septicemia, pneumonia, and endocarditis. In this study, a mixture of naloxone and alum has been used to improve the efficacy of killed methicillin resistant S. aureus (KMRSA) as a vaccine. Female Balb/c mice were divided into six groups and the vaccines were either injected alone, with naloxone, alum, or a mixture of naloxone-alum and control group received naloxone and PBS buffer. Total IgG antibody level was measured by ELISA method and finally, the challenge test of this bacterium was performed and the mice were examined regarding the degree of bacteria growth in their kidneys. The stronger immune response was observed when the vaccine was supplemented with a mixture of alum and naloxone and was able to decrease the number of bacteria in the kidney at the lowest level. The mixture of naloxone and alum as an adjuvant with the KMRSA enhances the humoral immunity leading to a high level of protection against MRSA infections