In an interview aired on Sunday, Mr Trump seemed to suggest an inevitability about the four star general's departure while adding that the two men had a "good relationship".
It is not the first time his exit has been discussed in Washington, although not publicly by Mr Trump, and just a few weeks ago the four star general was forced to dismiss reports of his impending departure.
But when asked during the CBS 60 Minutes conversation recorded on Thursday, if he thought Gen Mattis was heading for the door, the president was circumspect.
“Well, I don’t know. He hasn’t told me that. I have a very good relationship with him. I had lunch with him two days ago," he said.
“It could be that he is. I think he’s sort of a Democrat, if you want to know the truth. But General Mattis is a good guy. We get along very well.
"He may leave. I mean, at some point, everybody leaves. Everybody. People leave. That’s Washington.”
Reports have emerged during the last few months that Mr Trump is unhappy at the slow implementation of some of his military policies which he plants firmly at Gen Mattis's feet, including his ban on transgender servicemen.
And in September, the Washington Post reported that a list of replacements was being drawn up.
His departure may be hastened by claims made in Bob Woodward's explosive tell-all book that he told colleagues the US leader had the understanding of a "fifth or sixth grader" - a ten-year-old school pupil.
Should Gen Mattis leave imminently, he will be yet another high profile appointment to abandon the relatively young administration. Last week Nikki Haley, the US ambassador to the UN, announced her decision to leave at the end of the year.
When asked about the regular White House staff changes, often described as a revolving door, the president denied there was a retention issue.
"It's fake news.' he said. "I'm changing things around and I'm entitled to. I have people now on standby that will be phenomenal.
"I think I have a great Cabinet. There are some people that I'm not happy with. I have some people that I'm not thrilled with, and there are some people that I'm beyond thrilled with."