The crash happened on Mountain Road near Trimsaran in Carmarthenshire just before 23:20 BST.
One boy is at Glangwili Hospital in Carmarthen, and the other was taken to Cardiff's University Hospital Wales.
The road remains closed while investigations are carried out. Police have seized a second vehicle which was present at the scene.
Any witnesses are asked to contact Carmarthenshire Roads Policing Unit on 101.
Two 17-year-old boys suffered serious injuries when the car they were travelling in crashed on Sunday night.