The appearance Monday will be Obama's third time as president swapping jokes with Letterman, and his eighth appearance in all.
Michelle Obama took her final turn in the guest chair in New York Thursday night.
Noting his retirement, Letterman asked what she would do after leaving office in a year and a half. The first lady joked, "You mean whether I'm going to be running for president or anything?"
Mrs. Obama then offered to use her new free time to advise Letterman on raising his mercurial 11-year-old son, saying she knows what it's like because one of her two daughters can be a "grumpy cat."
Letterman's final show will be May 20.