The actor, who stars as Jamie Fraser in the popular historical drama, said he would "never say no" to making a cameo in the new show.
"I mean, I'll never say no," he told RadioTimes.com when asked if he would consider appearing in the upcoming spin-off. "But I think it could be pretty difficult as it’s about Jamie’s parents when they’re young."
He went on to add: "Unfortunately, Jamie can't time travel, as far as I know. Just Claire. But you never know. That's the joy of the show."
The spin-off, which was given the green light earlier this year, will consist of ten episodes and is set to explore "what lengths a person will go to find love in a time when love is considered a luxury, and when marriages are made strategically, often for political or financial gain," according to the synopsis.
"The title is a nod to Jamie Fraser's marriage vow to Claire and there will be several names and faces that 'Outlander' fans will know and recognise. Jamie and Claire's TV story may be coming to an end with season eight, but Diana is continuing on with their literary journey in her wonderful book series and is working diligently on book ten.
"With Jamie and Claire, and now Brian and Ellen, there is still so much more to come in the Outlander universe, and we cannot wait to continue sharing these stories with our dedicated fans."
Sam's co-star Caitríona Balfe hasn't ruled out a return to the Outlander universe after the show concludes with season eight.
During an interview with Decider, the Irish star reacted to a statement from executive producer Maril Davis, who said she's open to revisiting the story in the future.
Caitríona responded: "I think you never say never. The door's always open so we'll see."
Outlander will end with its eighth season and while fans are currently enjoying series seven, they may have to wait a little longer than expected to see the last episodes of the drama.
Caitríona recently shared an update on the production status of season eight, revealing that filming has yet to commence. "Well, we had a date. And now with the writers' strike, who knows? So we have to just wait and see," she told RadioTimes.com.
"That's obviously a big thing that's going on at the moment stateside and that may change things. But you know, it's too early to start speculating about that."
The final season will, of course, see Caitríona return as Claire Fraser, while co-star Sam reprises his role as Jamie Fraser. Viewers can also expect to see Sophie Skelton back on their screens as Brianna MacKenzie, as well as Richard Rankin as Roger MacKenzie, and John Bell as Young Ian.