The incident happened on the A82 between the Spean Bridge and Aonach Mor around 5.30pm on Monday, involving a white Audi A3, a black BMW 5 Series and a white Toyota Corolla.
A man and woman, both aged 21, were taken by air ambulance to the Queen Elizabeth University Hospital in Glasgow with serious injuries.
Another woman with serious injuries was also been taken by air ambulance to Raigmore Hospital in Inverness.
A 25-year-old man has been arrested in connection with suspected road traffic offences.
Road Policing Sergeant Angus Macleod said: “I am appealing to anyone who was in the area and saw these vehicles being driven before or during the crash to contact us.
“You can contact police on 101, quoting reference number 2550 of May 24.”