The death of a second child is being investigated by a special South Australian police task force already probing the alleged neglect of a six-year-old girl.
Police say task force Prime is now investigating the possible criminal neglect of a seven-year-old boy identified as Makai.
The two children are not related.
The boy was taken to Adelaide's Lyell McEwin Hospital in February this year, and later transferred to the Women's and Children's Hospital, but died the same day.
A post-mortem was conducted and identified several serious health issues, but they were not initially considered suspicious.
"The provisional cause of death, although it was unusual because you don't expect children to die, was not cause for immediate concern," Detective Superintendent Des Bray said on Monday.
The boy's death was reviewed in accordance with usual coronial procedures, but when further information was obtained from child protection authorities and after an opinion from a paediatric expert, police formed the view a criminal investigation was warranted.
"The role of the investigators, in this case, will be to review whether anyone is culpable for the death of Makai," Supt Bray said.
"Essentially, a case of criminal neglect occurs when a person who has a duty of care to a child fails to take all reasonable steps to protect the child from harm."
Supt Bray said in relation to the boy, it was believed neglect and abuse occurred over a period of time.
He said one person had been spoken to but had not been charged.
Task force Prime was established about two weeks ago to investigate the death of six-year-old Charlie, another case of alleged neglect.
Charlie was taken unresponsive from her mother's Munno Para home and died in hospital.
It was later revealed at least four SA government agencies - child protection, housing, human services and education - had interactions with the family over the past two years.
Premier Peter Malinauskas again pledged to support task force Prime in whatever way it could.
"One (death) was shocking, two is desperately heartbreaking for every parent across the state," the premier said.
"Two innocent children losing their lives, potentially because of criminal neglect. It's beyond sad.
"But we know about it and we have to respond."
Following Charlie's death, the state government launched a review by the premier's department into how government agencies handled the family's case.
But Mr Malinauskas has now decided to make that probe wholly independent of the administration.
The premier said former police commissioner Mal Hyde has been appointed to conduct the review.
"This is about making sure we have a review of integrity, of independence and robustness so we fully understand what interactions occurred between government agencies and these families," he said.
"To see whether or not there were failures of systems that could be addressed and should be addressed."
Mr Malinauskas said Mr Hyde's report would be made public.