Police media said local police attempted to resuscitate a 25 year old man after he was allegedly stabbed.

"Police received a call to a stabbing at 1.40am on Horton Street Port Macquarie," the police spokesperson said.

"Attending police tried to resuscitate the man who was also treated by attending local paramedics.

"The man was transported to Port Macquarie Base Hospital but died about two hours later."

A crime scene was set up and state crime officers and local police are investigating the stabbing.

"Police are searching for two men described as Caucasian in appearance and in their late teens or early 20s. Anyone with information should immediately contact their local police station or Crimestoppers on 1800 333 000."

* Amended: This article has been changed - the street involved is Horton not Gordon St.