It involved a single vehicle a silver Peugeot which was travelling towards Leeds.
The two male occupants, aged 31 and 33, had been ejected from the vehicle as a result of the incident. The fire service initially assisted in administering first aid and oxygen therapy to the casualties prior to them being taken to hospital with head injuries.
The male occupants remain in Harrogate hospital in a serious condition where they are being treated for head injuries.
The A61 road was closed for several hours while road traffic investigation took place.
The next of kin have been informed.
Police are appealing for witnesses or anyone who saw the vehicle prior to the crash or has any information relating to it is asked to contact:-
Traffic Constable Andy Macleod (andrew.Macleod@northyorkshire.pnn.police.uk)
or Traffic Sergeant Neale Rees (firstname.lastname@example.org) of the North Yorkshire Road Policing Group on 101.