The collision happened on the westbound carriageway between junction 23, Magor, and junction 24, Coldra, at about 15:25 BST.
Gwent Police said four people were believed to have been injured but the extent of their injuries is not known.
Earlier on Saturday, two people were taken to hospital following a crash at the same junction between a vehicle towing a horsebox and a motorbike.
That crash saw motorists face delays of up to 60 minutes as the exit slip road was closed - it was later reopened at 13:45.
The delays were not helped by the closure of the M48 Severn Bridge in both directions, which has been shut all weekend for maintenance work.
One lane of the M4 in Monmouthshire has reopened after a five-vehicle crash.