The collision happened at a level crossing outside the town of Perpignan at 4pm on Thursday afternoon.
Two of the victims are teenagers - one aged 13 and the other aged 17 - and another two youngsters are injured.
Transport Minister Elisabeth Borne has described it as a "terrible accident" and said on Twitter that she was heading to the scene - around 530 miles from Paris - immediately
"All emergency services have been mobilised and a crisis coordination unit set up," an official at the local Millas town hall said.
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