Police say the crash took place yesterday morning on the A267.
The incident involved a sewage tanker travelling northbound and a black Ford Focus travelling southbound.
The occupants of the car were seriously injured, but the lorry driver was not hurt.
Officers are urging anyone who saw what happened to email collision.appeal@sussex.police.uk quoting Operation Hales.
In particular, police are keen to hear from anyone who drove past but did not stop at the scene, who may have dash cam or mobile footage.