The 13-year-old and 14-year-old were among six children rushed to hospital following a "major incident" at a house in the Shiregreen area on Friday.
South Yorkshire Police previously said a 37-year-old man and a 34-year-old woman had been arrested on suspicion of murder.
Over the weekend the Crown Prosecution Service authorised the bringing of criminal charges against two people and police said: Two people arrested on Friday 24 May from a house in Shiregreen have now been charged and will appear at Sheffield magistrates court on Monday 27 May.
On Sunday, the force said: "Two people arrested on Friday May 24 from a house in Shiregreen have now been charged and will appear at Sheffield Magistrates Court on Monday May 27."
The four other children who were "rescued" from the house have now been released from hospital.
Detectives have given no indication about how they came to harm, but have confirmed it was not a shooting.
On Friday Det Ch Insp Simon Palmer said: A 37-year-old man and a 34-year-old woman have been arrested on suspicion of murder and remain in custody at this time.
People living nearby saw more than a dozen police cars and four ambulances arrive on the tree-lined road, and an air ambulance landed in the grounds of a nearby school.
The teens, aged 13 and 14, died in hospital on Friday after police were called to a “serious incident” at a semi-detached house