At approximately 5pm, three vehicles were involved in a collision on the A4146, between the roundabout at Billington Road and the roundabout with Grovebury Road.
Emergency services remain in attendance and the road is likely to remain closed for some time.
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Sergeant Nicholas Kane, from the Bedfordshire, Cambridgeshire and Hertfordshire Roads Policing Unit, said: “This was a serious collision which happened at a busy time of day, and we’re appealing for anyone who witnessed it to get in touch. In particular we’d like to speak to anyone who has dash cam footage of the incident.
“The road closure will be in place for some time while investigations are carried out, so we are advising motorists to avoid the area.”
Anyone with information is asked to contact police via www.bedfordshire.police.uk or by calling 101 and quoting reference number 324 of 8 March.