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The three-vehicle collision took place at 7.40am yesterday on the A361 between Burford and Lechlade, near the hamlet of Signet.
Thames Valley Police, South Central Ambulance Service and Oxford Fire and Rescue Service all attended.
The driver of the van, a man in his 20s, died at the scene.
Another man, in his 50s, was taken to hospital with serious injuries where he remains in a stable condition.
The third driver involved was not injured.
The road was closed near to Bradwell Grove for the rest of the morning to allow the police to conduct their investigation and it reopened in the afternoon.
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Investigating officer, PC Sandra Terry, of the Serious Collision Investigation Unit, said: “Our thoughts are with the family of the man who has died at this very difficult time.
“I am appealing to anybody who may have been in the area and witnessed this incident to please come forward.”
Fire and Rescue Incident Commander, Station Manager Nick Bourke, said: “Tragically, this serious Road Traffic Collision resulted in a fatality of the van driver and serious injuries to the lorry driver.
“Our thoughts remain with their family and loved ones at this devastating time.
“We support our police colleagues by asking anybody who was in the area at the time and witnessed the collision or may have dash-cam footage of the incident, to please contact 101, quoting reference 43200415646.”
He added: “On behalf of our service, I would like to pay tribute to the firefighters, policing and medical professionals who responded to this incident.
“We are sure you will agree that this is an extremely upsetting time for the family and friends of all those involved, the thoughts of all of us at Oxfordshire County Council Fire and Rescue Service are with the families at this difficult time.”
