Around 5.40pm the 32-year-old man was driving a Smart Roadster southbound on the B7078 Carlisle Road, Blackwood, when the vehicle was involved in a collision with a Ford Transit being driven northbound by a 61 year-old man.
Emergency services attended and the driver of the Smart car was taken by air ambulance to the Queen Elizabeth University Hospital in Glasgow where he is being treated for head and chest injuries.
Hospital staff describe his condition as serious.
The 61 year-old driver of the Ford was treated as the scene for minor injuries.
Sergeant John Tait of the Road Policing Unit at Motherwell is appealing for any witnesses to the crash, or anyone with information to contact his office through 101 quoting reference number 3025 of 13th August 2018.