The students, aged 15 and 16, accidentally received a whooping cough vaccine that is only meant to be given to pre-schoolers.
When administered to adolescents, the side effects can include redness, swelling, soreness and a high temperature.
Although there are no concerns for the long-term safety of the children, a full investigation has been launched by the Western Health and Social Care Trust.
It took two weeks for the WHSCT to notify worried parents at Omagh Academy in County Tyrone of the mistake.
In a statement, the Trust said: "Expert advice has been sought from the Public Health Agency, who have clarified that the vaccine that was given will still fully cover these pupils for all the diseases that the correct vaccine covered and they will not need to be re-vaccinated.
"The Trust takes this incident very seriously and has instigated an investigation into this error and will be taking forward all lessons learned as a priority."