Six people, including two children, were hurt in a crash involving three cars on the A27 near Lewes.
A Citroen Xsantia travelling east was involved in a head-on smash with a Renault Clio at the Beddingham roundabout at 3.10pm yesterday.
The Xsantia's 68-year-old male driver and 62-year-old female passenger were taken to the Royal Sussex County Hospital, Brighton, with serious injuries.
The driver and passenger in the Clio, both in their 30s, were also seriously hurt and taken to hospital.
Two children, aged seven and eight, suffered minor injuries.
Police said a third car, also a Renault Clio, was "slightly involved". No one inside was hurt.
The road was closed until 7pm.
PC Essex of Polegate traffic police is appealing for witnesses to call him on 0845 6070999.
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