Spanish Prime Minister Pedro Sánchez has said “the whole of Spain is grieving” and that “lives have been shattered, families have been torn apart”.
“The pain is immense,” he said on a visit to the crash site.
The government was “trying to determine what was the origin of this tragedy, of this terrible accident,” he added.
“We will get to the bottom of this, and if there has been any negligence, it will come to light.
“If there have been failures in the security system, they will be addressed with the utmost firmness.”
Sánchez and other Spanish politicians have cancelled all public engagements on Wednesday, including campaigning for next month’s parliamentary elections.
Three days of official mourning began on Thursday.
Spain’s royal family posted on X that it was “shocked and concerned” and expressed condolences for the relatives of the deceased and those affected by the crash.
A spokesperson for the EU said the bloc was ready to help Spain if needed.
A huge emergency response was under way with fire crews and helicopters at the scene.
Hospitals in the area have suspended planned surgeries as they deal with an influx of patients from the crash, Spanish media have reported.
A blood transfusion centre in Madrid has also appealed for “urgent” donations. In a post on X, Centro de Transfusión said it made the request “in the face of a possible sudden increase in care needs”.
It reported that facilities in Toledo, Ciudad Real and Alcázar de San Juan have cancelled procedures as casualties from the crash begin to arrive.
The Spanish Civil Guard has set up bureaus in Madrid, Toledo, Seville and Córdoba to investigate reports of missing persons.
“The top priority is the identification of the missing persons and the taking of DNA samples to be able to locate their relatives,” the civil guard wrote in a post on X.
This is the second high-speed rail tragedy in Spain this year.
In January a high-speed train derailed in southern Spain, its rear carriages going into the path of a state-run Renfe train, claiming the lives of 46 people.
