Six year old Josiah McIntyre, from Texas, died around a week after falling ill, while 13-year-old Tanner Lake Wall, from Florida, died days after swimming in a lake where he is thought to have contracted the amoeba.
The two cases follow a report in the NEJM of a 44-year-old dying from a brain eating amoeba after swimming in an indoor pool in India.
It emerged he had been swimming five days before the symptoms started.
This, the researchers wrote, is "almost universally fatal, although rare cases of survival have been described." The man died five days after arriving at hospital.
In Florida, Tanner's parents told News4Jax that their son had been swimming in a lake in a North Florida campground a few days before he fell ill.
He was then diagnosed with the brain eating amoeba N.
He has a parasitic amoeba, and there is no cure,'" his father Travis Wall told News4Jax.
Josiah, from Houston, became ill at the start of September, suffering from sickness and a fever.
His mother Maria said doctors initially thought it was a viral infection but she was later told he was suffering from a brain eating amoeba.
Speaking to Insider in June, CDC epidemiologist Jonathan Yoder said that in the first few decades where the amoeba was being tracked, it was only found in the southern tier of the U.S.