Detectives have launched a murder investigation after a man was fatally wounded in an incident in Queen Elizabeth Street.
Police officers and ambulance crews arrived and found a critically injured man.
The man, believed to be aged 20, was taken to hospital where he was pronounced dead at 3.45am.
"The area around Tooley Street has a popular nightlife and I would ask that anyone who had been to a club in the area and may have witnessed the assault to contact us," said Detective Chief Inspector Rebecca Reeves.
"A number of night buses also use this route and it is possible that someone travelling to work, or heading home, may have seen something that will assist our investigation."
Anyone with information is asked to contact the incident room at Lewisham on 020 8721 4868, or Crimestoppers anonymously on 0800 555 111.
Two men have been arrested in connection with the investigation and remain in custody at south London police stations.