Emergency services were called shortly after 3.10am on Monday, August 30, following an incident near the junction of the town’s Anderson Street and Ocean Road.
Police found a 19-year-old man who was unconscious.
He was given CPR by both officers and paramedics but sadly died of his injuries hours later.
The North East Ambulance Service have confirmed another male was also taken to South Tyneside District Hospital.
One man, aged 22, has now been arrested on suspicion of murder and remains in police custody at this time.
Two other men aged 20 and 23, have been arrested on suspicion of assault and also remain in custody.
A Northumbria Police spokesperson said on Monday afternoon: “A murder investigation has been launched after a man died following a serious assault in South Shields today.
“Our thoughts are with the man’s family and friends at this devastating time. They are being supported by specialist officers and we will continue to offer them any support they need. I would ask that their privacy is respected as they come to terms with their loss.
“We continue to carry out inquiries to understand the circumstances and, at this time, we are treating it as murder.
A spokesperson for the North East Ambulance Service (NEAS) earlier said: "We were called at 3.26am this morning to reports of people injured as a result of an incident outside Roxanne's nightclub, in Ocean Road, South Shields.
"Police also attended the scene along with three ambulance crews, an officer and a specialist paramedic.
"Two male patients were taken to South Tyneside hospital, one of which was in a critical condition."
The Northumbria Police spokesperson has urged witnesses to contact the force.
A statement added: “We understand that a number of people may have been present in Anderson Street at the time of the incident.
"I would appeal to anyone present there to come forward to us, calling 101 quoting log NP-20210830-0155 or Crimestoppers anonymously on 0800 555 111.”