O’Brien weds advertising executive Liza Powel in her hometown of Seattle, Washington. The couple met in 2000 during a skit rehearsal for the TV talk show host’s Late Night program and dated for 18 months before deciding to tie the knot. The ceremony is held at St. James Cathedral and officiated by the TV host’s friend and Harvard roommate, Fr. Paul O’Brien. On meeting his bride:
I did know very quickly. Somewhere in the vaults at NBC, there’s footage of me literally falling for my wife on camera. She’s incredibly beautiful. She’s very intelligent, and funny, and a really good person and so the nice thing is that, that was the basis of the relationship. So, I just knew.