Police were called at 2.15am to reports of a stabbing outside the Cubana restaurant in Lower Marsh, SE1.
Officers attended along with the London Ambulance Service. It was reported that a 32-year-old man had been stabbed.
At around 2.30am the man was found near to a block of flats in Frazier Street.
He was treated at the scene before being taken to hospital. Despite the efforts of emergency services, he died a short time later.
His next of kin have been informed and are being supported by specialist officers.
Detective Chief Inspector Brian Howie, who is leading the investigation, said: "A man has lost his life in the most tragic of circumstances and we will do all we can to track down those responsible. My thoughts are with his family and friends at this incredibly difficult time; they continue to be supported by specialist officers.
"While we are still in the very early stages of the investigation, we believe the victim was with a group of friends outside the Cubana Bar when there was some sort of altercation between two groups at around 2am. After being injured, he then made his way down Lower Marsh and onto Frazier Street.
"We know there were a lot of people in the area at the time, either socialising or returning home, or to local hotels, and I'm keen to hear from them about what they might have seen or heard.
"People in the area may have assumed this was just a pub argument, and thought nothing more of it. It may have been something that you thought was insignificant at the time, but it could be vital to our investigation.
“Did you hear raised voices or see the attack take place? Did you see anyone running away from the area? Did you film or photograph the attack? If so, we need to hear from you."
The man is yet to be formally identified and officers say they are not yet in a position to release his identity.
Anyone with information that could help the investigation is asked to call 101 quoting CAD 681/29Oct.
To remain anonymous contact the independent charity Crimestoppers on 0800 555 111.
On Saturday afternoon part of Lower Marsh and Frazier Street remained cordoned off, as did Waterloo Millennium Green. A police forensic tent was been erected outside the Cubana bar and restaurant.