A school bus carrying around 20 students from a local secondary school, was cut in half when it was hit by a train in Millas, about 18 kilometres west of the city of Perpignan, close to the Spanish border.
Passengers described the impact as extremely powerful, saying they feared the train was about to derail.
Around 95 emergency workers, backed by four helicopters were deployed as part of the rescue effort with the site cordoned off to the media.
The victims have been identified, a regional offical announced on Friday morning.
The bus driver was among the injured.
PM visits scene
French Prime Minister Edouard Philippe, who flew to the scene of the crash, said the process of idetifying the victims was extremely difficult, with 24 people caught up in the accident and 11 of them, mostly chidlren in a critical condition in hospital.
Transport Minister Elisabeth Borne called the crash a "terrible accident" and Education Minister Jean-Michel Blanquer was due to visit a counselling centre set up at the Christian Bourquin College on Friday.
"All my thoughts for the victims of this terrible accident involving a school bus, as well as their families," French President Emmanuel Macron declared. "The state is fully mobilised to help them."
Causes to be investigated
The reason for the crash is unknown. The national railway operator, the SNCF, quoted witnesses as saying that the level crossing was working normally.
The train driver was interviewed on Friday morning.
Borne on Friday morning said an interministerial coordinator would be named to help the victims' families.
An investigation into the causes of the crash has been ordered.
"In 98 percent of cases, it is a road-safety error that is the cause of these accidents," she said.
A source close to the enquiry said witness questioning was underway and the drivers of the bus and train would be tested for alcohol and drugs.
There were 31 deaths on France's 15,000 level crossings in France last year and there had been 33 this year, until Thursday's accident.