Officers attended the fatal two-car crash near Slindon just after 12.30pm on Friday (August 27).
The driver of one car – a woman in her 80s – was confirmed dead at the scene on the A29 at Fairmile Bottom.
A Sussex Police spokesperson said: "The man driving the other car was taken to hospital to be treated for injuries. Nobody else was reported involved.
"Police are particularly keen to hear from the driver of a white vehicle – possibly a Mercedes – who stopped and spoke to one of the drivers involved.
"This person may be a key witness to the events leading up to the collision."
Police officers would also like to speak to any occupants of a light, 'possibly silver or white', coloured vehicle that was travelling northbound.
It is believed to have turned around and travelled back south after the crash, police said.
"They may be one and the same vehicles, but police are keen to confirm the details to assist with their investigation," the spokesperson added.
"Anyone with any information about the collision is asked to email [email protected] or 101, quoting Operation Dordrecht."