A woman and an 11-year-old boy were taken to hospital with serious injuries following a crash on the A27 in Shoreham.
A white Vauxhall Vivaro and a red Peugeot 308 collided at the crossroads with Coombes Road shortly before 5.30 on Monday morning.
The Peugeot driver – a 50-year-old woman – and her passenger – an 11-year-old boy – were both taken to Royal Sussex County Hospital in Brighton.
The Vauxhall driver – a 39-year-old man – was taken to the same hospital with minor injuries.
The eastbound carriageway was closed until about midday while investigations and recovery were carried out but has since reopened.
Sussex Police are appealing for witnesses or anyone with dash cam footage of the incident to report it online or call 101, quoting Operation Fairmile.