Police were called at 12.55pm today to reports of a collision in the Southwick Tunnel heading westbound, with one vehicle understood to be just inside the tunnel, and another just outside.
The westbound carriageway has been closed by police, and the Hangleton slip road onto the A293 while the emergency services deal with the incident.
A police spokesman said: "Police closed the A27 Shoreham by-pass westbound between its junction with the A293 at Hangleton and Southwick Hill Tunnel where three vehicles had been in collision.
"The outer lane of the dual carriageway re-opened at 1.37pm and the A27 was fully re-opened at 2.38pm.
"No serious injuries were reported, although two casualties - believed to be a 10-year-old girl and a teenage boy - were taken to the Royal Sussex County Hospital, Brighton, for further checks."
A spokesman for the South East Coast Ambulance Service said: "We were called just before 1pm today following reports of a multiple-vehicle collision. We assessed and treated six patients at the scene – three of which were taken to hospital.