The A27 was closed for several hours near Wilmington last night.
Emergency services rushed to the two-car collision at the Wilmington crossroads just before 5.50pm.
An ambulance service spokesperson said paramedics treated two people at the scene – one for head and neck injuries.
They were taken to Royal Sussex County Hospital in Brighton while another casualty with less serious injuries was taken to Eastbourne District General Hospital, SECAmb (South East Coast Ambulance) said.
The A27 was closed for several hours following the incident where The Street and Thornwell Road join the busy road.
Sussex Police were also called to the scene.