A pedestrian, thought to be in his 20s, was killed on the A142 near Stuntney and a 66-year-old man died on the M11 near Madingley, both early on Sunday.
Later, a biker died on Fletton Parkway in Peterborough, and an 88-year-old man in Milton Road, Cambridge.
A man in his 70s died in Little Downham on Friday and a driver is in hospital after a crash in West Wratting.
Witness appeal
Cambridgeshire Police said they were investigating the accidents and have appealed for witnesses and information.
The first collision happened at 0130 BST on the A142 near Stuntney when a car driven by a 48-year-old man from Ely hit a pedestrian, believed to be in his 20s.
The second took place at 0215 BST on the southbound carriageway of the M11 near Madingley when a lorry hit a 66-year-old pedestrian from the Cambridge area who died later in hospital.
A 37-year-old motorcyclist from Northamptonshire was killed on the eastbound carriageway of the A1139 Fletton Parkway in Peterborough, in the third accident.
In the fourth an 88-year-old man died after he was in collision with a motorcycle on Milton Road in Cambridge.
On Friday evening a driver in his late 70s died when his Volvo V40 car left the road on Cannon Street at the junction with Church Street in Little Downham.
"The serious injury crash happened on Sunday afternoon and involved a Citroen Saxo and a Ford Fiesta near The Common in West Wratting," said a police spokesman.
"The Citroen driver, a man in his 20s from Bedford, suffered life-threatening injuries and was taken to Addenbrooke's Hospital in Cambridge where he remains in a critical condition."
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