Introduction: Vaccination is one of the most effective ways to control the COVID-19 pandemic. However, as the number of people vaccinated against COVID-19 continues to increase, there are more reports on the safety of vaccines. So far, there have been no reported cases of spinal infection associated with COVID-19 vaccination. Recently, we admitted a patient who developed cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine when the symptoms of cold did not completely disappear. Case presentation: The patient was a 70-year-old man who received the third injection of COVID-19 vaccine when the cold symptoms were not completely gone. On the day after the injection, the patient developed severe neck and shoulder pain, accompanied by numbness and fatigue in the limbs. MRI examination of the cervical spine on day 6 after vaccination showed no obvious signs of infection. The patient had progressive weakness in the extremities. On the ninth day after vaccination, the patient developed paralysis of both lower limbs and significant sensory loss. Cervical abscess and cervical spinal cord injury were considered for cervical CT and MRI examination on the 15th day after vaccination. We used an anterior approach to remove as much of the lesion as possible. Staphylococcus aureus was detected and antibiotic treatment was continued after surgery. The patient’s pain symptoms were significantly relieved, which prevented the abscess from further pressing the spinal cord and provided possible conditions for the recovery of neurological function in the later stage. Conclusion: This case is the first reported cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine with low immunity. This case raises awareness of this rare but potentially life-threatening adverse reaction, and reminds people to hold off when their immune system is weakened.