The 56-year-old man was discovered with a serious head injury after midnight in Miller Street, Merchant City, close to pubs and clubs busy with revellers.
He was taken to the city's Southern General where he has now regained consciousness.
It is unclear if the man was attacked or if he fell and officers are appealing for witnesses.
They would also like to speak to a man who went to the injured man's aid.
Detectives are gathering CCTV images to try to establish what happened.
Detective Inspector Sandy McLean, said: "It is important we find out what happened to him. He has suffered a serious injury and we are carrying out enquiries to find out what has happened.
"There are residential flats near to where the man was found and I would appeal to anyone who may have seen or heard anything to get in touch with us."
The man is the second person found unconscious and injured in a city centre street in a week. Detectives are still investigating an incident which left another man with a serious head injury.
The 47-year-old was discovered on a path between Trongate and Saltmarket at around 9pm on Tuesday.
Paramedics treated the man before taking him to the Royal Infirmary. His condition was described as serious but stable.
Anyone with information on either incident should call 0141 532 3000.