Northumbria Police has sealed off a short stretch of Borough Road in the city centre after the incident this afternoon.
The road is closed between Kwik Fit, at its junction with Toward Road, and the Golden Chef takeaway.
Officers are in attendance but there is no sign of any forensic investigation under way.
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A North East Ambulance Service spokesman said the Great North Air Ambulance had been called but the man was taken to Newcastle’s Royal Victoria Infirmary by road: “We received a call at 3.39pm to a report of a man who had been punched and then fallen in the road unconscious.
"We dispatched one ambulance, a rapid response paramedic and the air ambulance.
"We treated a patient with head injuries before transporting him to the RVI.”
Mollik Ahmed, who runs Perfect Fried Chicken in Borough Road, said he had seen a man with head injuries lying in the street when he arrived for work this afternoon.
"It was about half past three, quarter to four,” he said.
"I saw him lying there and went to help. There were already a few people in the road who were trying to help him.
“I asked if I should call the police and an ambulance but two ladies said they had already phoned.
"The ambulance arrived straightaway and they started working on him.
"It was very sad.”