The boy was taken from a home in Velville Court in Newcastle to hospital with serious injuries, on Friday.
A 34-year-old man and a woman, aged 30, are currently in police custody and are due to be questioned.
Northumbria Police said the baby died on Monday and officers are treating the injuries he had suffered were "non-accidental".
Det Ch Insp Mark Ord said: "We are treating the death as a homicide investigation.
"We know this will shock and sadden the local community and I would like to reassure them we are doing everything we can to establish exactly what happened and how the baby came to suffer such fatal injuries.
"This is a very tragic incident and our thoughts are with all those affected by this sad death."

It has shared details of the mission that led to America's most-wanted man being found five years ago in Pakistan.
But reaction has been largely negative, with one Twitter user calling the move "grotesque and embarrassing".
Others posted memes and gifs of people rolling their eyes and putting their heads in their hands.
The CIA's other tweets mostly concern historical trivia and artefacts.
How the lives of Osama Bin Laden's neighbours changed forever
Legacy of Bin Laden's death
Who was Osama Bin Laden?
Bin Laden's death: How it happened
Have we been told the truth about Bin Laden's death?
The leader of al-Qaeda, who was thought to have ordered the 9/11 attacks on New York and Washington, was shot dead at a compound in Abbottabad, in May 2011 after evading capture by the US and its allies for nearly a decade.
Speaking on the fifth anniversary of his death, CIA director John Brennan said the United States had destroyed a large part of al-Qaeda.
Bin Laden had a great symbolic and strategic significance, he told CBS, and it was important to remove the man responsible for the 9/11 attacks.
He said removing the head of the self-styled Islamic State, Abu Bakr al-Baghdadi,  could have a great impact but added that counter-terrorism agencies were confronting not just an organisation but a phenomenon, and the challenge would continue for many years.
"I think it has had a resonance, unfortunately, that has appealed to the hearts and souls and minds of individuals who have been misled by their narrative of it being a religious banner," he said.
Two people have been arrested on suspicion of murder after a 13-week-old baby died.
[NEXT_CONCEPT]
The US Central Intelligence Agency (CIA) has been criticised online for live-tweeting the killing of Osama Bin Laden as if it were happening today.