An 8-year-old Guatemalan boy died Christmas morning in the custody of US Customs and Border Protection, the agency said.
He is the second Guatemalan child to die in CBP custody this month.
The boy, who was detained with his father, died shortly after midnight at Gerald Champion Regional Medical Center in Alamogordo, New Mexico, about 90 miles north of the border crossing in El Paso, Texas.
He was taken to the hospital Monday after a border agent noticed signs of illness, and the medical staff first diagnosed him with a common cold and later detected a fever.
"The child was held for an additional 90 minutes for observation and then released from the hospital mid-afternoon on December 24 with prescriptions for amoxicillin and Ibuprofen," CBP said in a news release.
Amoxicillin is a commonly prescribed antibiotic.
On Monday evening, the boy began vomiting and was taken back to the hospital for evaluation. He died hours later, the CBP said.
The official cause of death is unknown. CBP is conducting a review and will release more details as they become available, it said.
The Guatemalan government has been notified and is in touch with the father and family members in Guatemala, CBP said.
The CBP news release says the Department of Homeland Security is experiencing "a dramatic increase in unaccompanied children and family units arriving at our borders illegally or without authorization," and per law, holds such individuals at federal facilities until they are deported or released into the United States with a notice to appear in court.
"During their period of detention they received medical screenings and further treatment as needed," it said.
A 7-year-old girl, Jakelin Caal Maquin, fled Guatemala with her father, and after surviving the 2,000-mile journey to New Mexico, she died December 8, fewer than 48 hours after CBP detained her and her dad.
Her body was repatriated Sunday to Guatemala, and her remains were to be transported to the indigenous community of Raxruha, where she called home.
Her death marked another flashpoint in the debate over the White House's hard-line approach to immigration enforcement, with many -- including Jakelin's family -- wondering if better medical care may have saved her.
Felipe González Morales, the UN special rapporteur on the human rights of migrants, said Monday that American authorities "must ensure that an in-depth, independent investigation" is conducted.