A car and a motorhome collided on the A4620 yesterday evening.
A woman in her twenties suffered life-threatening injuries in the crash.
A teenage girl, a woman in her fifties and a man in his fifties were also seriously hurt, whilst a teenage boy and another woman in her fifties suffered minor injuries.
The collision happened near the Sturdys Castle Hotel at around 6:30pm involving a black Peugeot 5008 and a white motorhome.
Police say the casualties with life-threatening or serious injuries were taken to the John Radcliffe Hospital in Oxford for further treatment, where they all remain.
Investigating officer PC Liam Calvert from the Joint Operations Roads Policing Unit based at Bicester, said: “I am appealing for witnesses to this collision to please come forward.
“Also, if you have any dash-cam footage if you were driving in the area around the time, I’d also ask that you check any recordings in case it has captured something that could assist our investigation.”
Witnesses should call 101 or make a report online, quoting reference number 43220348824.