Detectives have established a crime scene at the Grosvenor Hotel on Phillip Street, where the 52-year-old man was reportedly assaulted on Tuesday afternoon.

His death came a day after another man, father-of-one Kyle Watkins, died in hospital following a one-punch attack in Coffs Harbour.

In the latest attack, a NSW Police spokeswoman said detectives had been told the man was at the hotel in Waterloo when he was assaulted by an unknown person about 4pm.

The exact circumstances of the confrontation were not clear, however police had been told the man was struck on the head, fell to the ground and went into cardiac arrest.

A NSW Ambulance spokeswoman said paramedics were called to Phillip Street about 4.15pm to treat the man. He was taken to St Vincents Hospital in a serious condition.

Police said the man died in hospital about 1.30am on Wednesday. Hospital staff notified police, and detectives from Redfern Local Area Command are now investigating.

On Wednesday morning detectives established a crime scene at the hotel and forensic officers were examining the area. Police were investigating whether the attack was captured by a CCTV camera.

Mr Watkins, 27, died in hospital after he was punched in Coffs Harbour, on the NSW north coast. His life support was turned off on Tuesday following the attack on West High Street on Saturday night.

Friends described Mr Watkins, who had a young son, as a good father and a "kind soul".

"In school he was that boy who was nice to those being bullied, he was nice to everyone," a Facebook post said. "My heart goes out to his family... Fly high KW."

Mr Watkins, from the small town of Ulmarra, about 95 kilometres north of Coffs Harbour, had been at a licensed premises in Coffs Harbour with friends.

Police said he left about 10.15pm and was walking west along West High Street, near the intersection with Lyster Street, when he and another unidentified man became involved in an argument.

Police say the unidentified man threw a punch, causing his victim to fall to the ground and hit his head on the road. The attacker ran from the scene while his victim lay unconscious on the road.

Mr Watkins was taken to Coffs Harbour Hospital with critical head injuries. He was later flown to John Hunter Hospital, where he died about midday on Tuesday.

Police are appealing for anyone with information about either assault to contact Crime Stoppers on 1800 333 000 or visit the Crime Stoppers online reporting page.