A further five were injured in the southern town of Nove Zamky, 68 miles east of the capital, Bratislava, emergency services said on Facebook.
The train’s engine was on fire, video footage showed, while the bus was badly damaged, railway officials said.
More than 100 people were on board the Eurocity service when the accident happened shortly after 5pm local time (4pm BST), railway company ZSSK said.
It was traveling from the Czech capital, Prague, to the Hungarian capital of Budapest.
Dozens of stranded passengers are being taken by bus to the town of Sturovo on the Hungarian border, ZSSK said.
Interior minister Matus Sutai Estok is heading to the crash site, police said.
The main railway track linking Bratislava and Budapest has been closed.
Peter Pellegrini, the president of Slovakia, offered his condolences.
“I wish the injured a speedy recovery and thank the doctors and rescue teams for their work,” he said.
“I wish that such catastrophes would avoid Slovakia in the future.”
