A 38-year-old man, who was a rear seat passenger in the car, suffered serious injury to his stomach and abdomen and was taken to Edinburgh Royal Infirmary (ERI) where he is in a critical but stable condition.
The 58-year-old man driving the car suffered spinal injuries and a fractured ankle, and the 34-year-old man in the front passenger seat suffered face and leg injuries. Both were taken to ERI.
The crash between a single-decker First bus and a southbound Vauxhall Zafira happened on the B9080 between Kirkliston and Winchburgh.
The driver of the bus, which had 26 people on board, had to be cut free by firefighters following the crash at around 10.15pm yesterday.
Three passengers on the bus were also taken to hospital with minor injuries, including a woman who was complaining of chest pain, but all have since been discharged.
The driver and six other passengers were treated for various minor injuries.
Police appealed for information about the crash.
Road policing sergeant Ross Drummond said: "This incident has resulted in a number of casualties, some of whom have suffered serious injury.
"We are keen to hear from other motorists who were on the B9080 on Wednesday night and who may have witnessed the collision take place.
"In addition, anyone with any further information relevant to our ongoing inquiries is also asked to contact police immediately."