A white Peugeot van and a black Mercedes estate car were involved in a collision on the A40 Oxford Road at the junction with Chips Hill at about 4.10pm on Saturday (28/7).
The driver of the Mercedes, a man in his fifties, suffered serious injuries and was taken to the John Radcliffe Hospital, where he remains.
A passenger from the Mercedes and the driver of the Peugeot also sustained serious injuries and were taken to Wexham Park Hospital, where they remain.
Investigating officer, Police Constable Tom Smith of the Roads Policing Unit, said: "I am making a specific appeal to the occupants of a black BMW and a grey Renault who I believe may have witnessed the collision.
"If you were in these vehicles, or have any information about the collision please contact police as soon as possible because your information could be vital in this case.
"The easiest way to contact police is by visiting our website at https://www.thamesvalley.police.uk/tua/tell-us-about/cor/tell-us-about-existing-case-report/ or by calling us on 101, quoting reference 43180231215."