Emergency services were called to South Road, High Green, at about 1am on Saturday (Jan 30) to reports of an assault.
A 45-year-old man was found with serious injuries and he was pronounced dead while being taken to hospital.
South Yorkshire Police have arrested a 19-year-old woman and a 25-year-old man on suspicion of murder.
Both remain in custody this afternoon.
Formal identification of the 45-year-old and a post mortem examination are yet to take place.
South Yorkshire Police say there will be a police presence in the High Green area of Sheffield as officers carry out enquiries into the circumstances surrounding the man’s death.
Anyone with information is urged to call 101 quoting incident number 54 of January 30, 2021.