Karen Gillan and Arthur Darvill - who play Doctor Who companions Amy Pond and Rory - are to leave the show during the next series.
Doctor Who boss Steven Moffat made the announcement at a screening of the Christmas episode at BBC TV Centre in London.
"The final days of the Ponds are coming," Moffat said.
"I'm not telling you when or how, but that story is going to come to a heartbreaking end."
He said the Doctor, played by Matt Smith, was going to meet "a new friend". It is believed that role has not yet been cast.
On the departure of Gillan and Darvill, Matt Smith said: "We had the most incredible journey. We took over the show and we've really had to hold hands and help each other through it.
"So it's very disappointing, but one has to remember that this show is about change and regeneration, and that's what galvanizes it and pushes it forwards."
The Christmas Day special - titled The Doctor, The Widow and The Wardrobe - sees the Time Lord go on an adventure with Madge Arwell (Claire Skinner) and her two children, Lily and Cyril, when they are evacuated from London to Dorset during World War II.