Two regional trains were involved in the incident near Bad Aibling, in Bavaria, according to reports.
One train is reported to have derailed in the accident, with several carriages overturned.
Police spokesman Stefan Sonntag told reporters two regional trains crashed head-on on the single track, suggesting a signal failure.
It happened between Rosenheim and Holzkirchen shortly before 7am local time.
Eight rescue helicopters were involved in rescue efforts near Bad Aibling, with further emergency staff making their way to the site.
Mr Sonntag said at least two people had died in the crash, but that the scene of the accident is so chaotic, there are no specific numbers over the amount of dead or injured.
"This is the biggest accident we have had in years in this region and we have many emergency doctors, ambulances and helicopters on the scene," Mr Sonntag said.
He added that some people are still trapped inside the wreckage, and rescue personnel are trying to free them.
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