Bedfordshire Police is appealing for witnesses following the collision, which happened on the A505 at about 9am.
Officers were called to reports of a crash between a Volkswagen Golf and a van, with a man in his 20s confirmed to have died at the scene. His next of kin have been informed.
A Bedfordshire Police spokesman said: "The road remains closed, and will remain closed for a period of time, while officers investigate and clear the scene.
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"Investigating officers are seeking the public’s help as they look to establish the cause of the collision."
Detective Sergeant Ben Heath, from the Bedfordshire, Cambridgeshire and Hertfordshire Serious Collisions Unit, said: “We are appealing to anybody who witnessed this collision to get in touch with us as soon as possible.
“If you were in the area at the time or have any dashcam footage of the incident or leading up to the incident, please get in touch”
If you have any information that could help the investigation, please call 101 and quote Operation Science.
The incident comes just weeks after a petition was submitted to Central Bedfordshire Council, calling for the bypass to be made safer.