A 17-year-old has been arrested following the fatal stabbing of a man in Coffs Harbour overnight.

Shortly after 1am, emergency services were called to an address on the Gwydir Highway across from Hay Street.

They found a 35-year-old man with significant stab wounds to his upper body.

Coffs-Clarence Police Detective Chief Inspector Guy Flarety said that despite the best efforts of emergency responders, the man died shortly after 3am.

Police arrested a 17-year-old who has been assisting in police inquiries following the incident.

Multiple items were collected from the scene by police, including a knife, which police suspect was used in the attack.

Investigators believe a potential altercation that took place an hour earlier on Bent Street may be connected to the attack.

Police say the people involved were likely known to each other and fled the scene shortly after on motorbikes or quadbikes.

The highway remains closed as investigations continue.

Anyone with information is urged to contact Crime Stoppers on 1800 333 000.