Two boys have died and four other children are in hospital following an incident at a house in the Shiregreen area of Sheffield.
The two boys, who were both pupils at Firth Park Academy, were aged 13 and 14, South Yorkshire Police said.
A 37-year-old man and a 34-year-old woman have been arrested on suspicion of murder in connection with the incident and remained in custody.
Police said the four injured children were conscious but remained in hospital.
Detectives refused to discuss the relationship of the people in custody with the victims, but said they were not looking for anyone else in connection with the incident.
A spokesman for South Yorkshire Police said officers were called to the property at around 7.30am on Friday after a third party expressed concern for the welfare of those inside.
Yorkshire Ambulance Service and Yorkshire Air Ambulance attended the scene and transported six children to hospital.
The incident took place close to the Hartley Brook primary school and witnesses reported seeing the air ambulance land in the grounds of the school.
Local residents claimed they had seen two children being taken out of the house by paramedics before being rushed away in an ambulance.
They also reported seeing a man and a woman being taken away from the property in handcuffs.
There were initial reports that the incident involved firearms, but South Yorkshire police denied that there had been a shooting.
We can confirm that this is not a shooting— SouthYorkshirePolice (@syptweet) May 24, 2019
Crime scene investigators were spotted arriving at the scene shortly after 10.30am.
Detective Chief Inspector Simon Palmer said: "Detectives and specialist officers remain in the Gregg House Road area carrying out inquiries and we are working hard to ascertain the exact circumstances surrounding this incident.
It is understood the youngsters were taken to The Sheffield Children's Hospital in the Broomhill area of the city.
It is understood the two dead boys were pupils at the Firth Park Academy close to the scene.
A statement posted on the school's website read: "It is with great sadness that we can confirm that two of our students, died in tragic circumstances this morning.
"As this is a Police matter, we are not able to provide any further detail at the moment. Our deepest condolences are with the family and their friends during this difficult time.
"We will be providing the appropriate support to our students and staff to help them to come to terms with what has happened. Terrible things can happen in life and there are specialists there to help and who are now helping. We must all look after each other."
Jonathan Campbell,50, who lives a few doors up from the house where the incident took place, spoke of his shock.
He said: "The police knocked on our doorstep and told us there had been a domestic. It was quite a shock to see so many police cars and ambulances outside. I saw a baby of about six months old being carried to an ambulance by a paramedic.
"I had never seen the kids or the parents before - they can't have lived here long
Mick Whittaker, 61, milkman who has lived on the same street for 11 years, said: "I pulled up from my round at about 8am and there were sirens wailing down the street. Twenty minutes later the air ambulance landed in Hartley Brook school.
"I didn't know the family and asking around it seems nobody did. There have been sirens down that end of the street before but this is horrific."