A police cordon has been erected near the premises of Jack Wills, Fat Face and Sweaty Betty half way along the busy city centre thoroughfare.
Officers confirmed that a serious assault took place at around 3.20am on Wednesday morning on George Street close to the junction with Frederick Street.
A 39-year-old male received serious head and facial injuries after being approached and subsequently attacked by two men.
The victim was initially taken to the Edinburgh Royal Infirmary but has since been transferred to the Western General.
It is understood that the suspects made off on foot down Frederick Street.
They are both described as white males, wearing dark coloured clothing.
One of the suspects is described as between 30-40-years-old, around 5ft 11ins tall and was wearing a black puffa jacket.
Forensics are currently on the scene at George Street.
Detective Inspector Grant Johnston from Gayfield CID said: “Our inquiries are ongoing to establish the full circumstances of this incident, and I am keen to hear from anyone who witnessed what happened to come forward.
“I would especially like to hear from anyone who may have seen the victim or the suspects before the incident.
“Anyone with any information to assist our inquiries and in tracing those involved,is asked to get in touch immediately.”
The bus lane eastbound has been closed off.
Shops on George Street are still accessible to pedestrians.
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