The latest probe was launched yesterday following the discovery of a seriously injured man on Fretson Green, Manor, at 12.34am yesterday.
Emergency services were deployed but the man was pronounced dead at the scene and a hunt for his killer was mounted.
A huge police cordon was erected around the crime scene, just yards away from a children’s playground.
Shocked residents woke yesterday to find their streets taped off and under police guard as crime scene investigation work was carried out.
Detective Chief Inspector Mark Oughton, leading the police investigation, said there will be a large police presence in the area for a number of days.
In addition to carrying out door-to-door enquiries, a CCTV trawl and searching for witnesses, officers will also be carrying out reassurance work in the shocked community.
Residents voiced concerns about crime on the Manor estate in the wake of the murder, with one woman who lives on a street where a gun was fired earlier in the year calling for extra police patrols.
DCI Oughton said: “I know this incident will concern the community who live in the Manor area and I’d like to reassure the public that we are doing all we can to find those responsible.
“There will be significant number of officers in the area over the coming days, they will be continuing with house-to-house enquiries and searches.”
The nature of the dead man’s injuries have not yet been released by South Yorkshire Police.
He has also not yet been named by the force.
The murder came in the same week that a 30-year-old man was shot dead in Sheffield.
Khurm Javed, a solicitor and dad-of-two, was gunned down on Clough Road, near Bramall Lane, on Saturday, April 10 following a ‘confrontation between two parties’.
Two arrests have been made over that killing but nobody has yet been charged.
Anyone with information about the latest murder should call South Yorkshire Police on 101 and quote incident number 29 of April 17.
Crimestoppers can be contacted, anonymously, on 0800 555111.