Officers responded to reports of a man lying in Bridge Street, Girvan, at about 02:30.
The 23-year-old was taken to Crosshouse Hospital in Kilmarnock then later transferred the Queen Elizabeth University Hospital in Glasgow.
Police have appealed for witnesses to come forward.
Det Insp Alan Sommerville said: "We understand that there was a disturbance on Bridge Street in the early hours of Monday morning which has left a man seriously injured.
"Anyone who witnessed any suspicious behaviour on Bridge Street at the time of the incident is asked to contact Ayr Police office."
Police in South Ayrshire are treating an incident where a man was found seriously injured in the street as attempted murder.