The pair have confirmed they will be leaving after the current run, with their last ever shows going out on BBC Two on 26 February.
Sarah, who made her fortune with The Bombay Bicycle Club restaurant chain, and Nick, who is the founder of Moonpig.com, joined the show in 2015.
The other Dragons - Deborah Meaden, Peter Jones and Touker Suleyman - are all believed to be staying on for the next series.
Speaking about her departure, Sarah said: “Being part of Dragons’ Den has been one of the best experiences of my life.
“At the end of last year my husband Michael and I decided to finally put into action our long-held dream to spend a year travelling the world with our young children.
“Sadly this means that I’ve had to step down from my role as a Dragon. It’s been a great privilege to be part of such a fantastic show and I wish everyone on it continued success.”
Meanwhile, Nick Jenkins said he wanted to focus more time on his various businesses.
He said: “I have thoroughly enjoyed making Dragons’ Den but I want to focus more on my portfolio of educational technology businesses and that would make it difficult to take on any more investments from the Den.”
Patrick Holland, channel editor at BBC Two, said: “Nick and Sarah have both been terrific Dragons, using their nous and insight to make some great investments and produce some compelling entertainment in the process.
“As they step down from the show I want to thank them and wish them all the very best for the future.”