In last night's 100th instalment of the show, Blair (Leighton Meester) fled from her wedding reception with Dan (Penn Badgley).
Safran has now revealed that the next episode will be a "direct pick-up and is the same night", TV Guide reports.
Safran added that viewers will discover where the duo went in the next episode.
"They go some place we've never shot before, but have always wanted to shoot," he teased. "It was really complicated but a super-fun, big, great set piece. And it also has, in my mind, some of the best comedy we've ever done. The next episode is very funny."
Safran also revealed that Dan may become fed up with Blair always turning to him in her times of need, saying: "At a certain point he probably won't be able to stand feeling that anymore and force Blair to not treat him that way - or not treat him at all basically."
He added that Serena (Blake Lively) and Chuck (Ed Westwick) may not be happy about Blair and Dan's escape.
"You're going to see them learn, you're going to see what they do about it, how it impacts them," he said. "Definitely the story of that next episode is Chuck and Serena together dealing with Blair and Dan together."
Gossip Girl airs on Mondays at 8/7c on The CW.
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Watch a promo for the next episode of Gossip Girl below: