Some 100 passengers were on the train when at least two carriages partially derailed. Around 50 are injured, a number of them seriously, according to the district fire chief.
The cause of the derailment is still unclear, but the region was hit by a storm earlier in the evening.
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German police said on Monday that the derailment in southwestern Baden-Württemberg state was likely caused by a landslide triggered by heavy rains.
"The water triggered a landslide in the embankment area near the tracks, which in turn probably caused the derailment," investigators said.
The derailment came after the region had been hit by a storm over the weekend.Investigators said that at least 41 people had been injured according to the latest information available.
Officials had said in an earlier count that some 50 people had been injured.
Also on Monday, Germany's weather service (DWD) warned of continued heavy rain in Baden-Württemberg, with the showers reaching 20 to 30 liters per square kilometer (around 13.7 to 20.5 gallons per square mile).
Local police say that all of the injured have been transported from the scene of the train crash to surrounding hospitals.
DW's Michael Watzke, who reported from the scene early on Monday morning, said that the remaining passengers had been brought to a community center in a nearby village.
He said that the crash site was still a hive of activity.
Videos show hundreds of people, including firefighters, police, train workers and even the army helping at the scene of the accident as generators hum in the background.
Rescue workers with dogs were also checking that none of the passengers were trapped under the derailed carriages, Watzke said.
He added that there are plans to bring in heavy cranes on Monday to lift up the carriages.
The regional express was pulling four carriages, he said, when it derailed.
Richard Lutz, the chief executive of Germany's national rail operator Deutsche Bahn, said that everyone at Deutsche Bahn is deeply shocked and dismayed by the accident.
"My heartfelt sympathy and condolences go out to the relatives of the deceased. I wish the injured a quick and full recovery," he said, thanking all the emergency services and volunteers on site.
Lutz also said that he would visit the site of the accident on Monday.