Police, fire and ambulance services were called at around 10.30pm on Friday to reports of a large blaze at a former station house in Beswick Close in Rushton, near Kettering.
Three people were later confirmed to have died, Northamptonshire Police said. No further details on the identity of the victims have been given.
Three police officers required hospital assessment because of smoke inhalation, the force added.
The cause of the fire is now under investigation by police and Northamptonshire Fire and Rescue Service.
Photographs show a large hole burned through the roof of the building – a 19th-century former station master’s house at the now-closed Glendon and Rushton railway station.
It is a Grade II-listed building, according to the Historic England website, and is now believed to be a residential property.
Train services between London St Pancras International and Corby, Derby, Nottingham and Sheffield were disrupted, along with services between Kettering and Nottingham after the fire, which was near a railway track.
The disruption was due to damage caused to a railway line, according to the National Rail website.
