The Reverend Dr Angus Morrison, a minister in Perth and Kinross, was due to take office in May.
The 60-year-old revealed he had taken the “very painful” decision to walk away from the job as he is having medical treatment and may need surgery.
The Kirk said he was the first moderator-designate in living memory to stand down.
The minister of Orwell and Portmoak Church in Milnathort said: “This has been a very painful decision but deep down I feel it is the right one. I am undergoing medical treatment and anticipate an operation ahead.
“The demanding role of moderator requires someone to be operating on all cylinders. I do not have the necessary reserves just now.
“It is with huge regret and reluctance that I make this decision. My heartfelt prayers will be with all those on whom unexpected burdens now fall.”
The short notice raises the possibility the Kirk could be forced to break with its long-held tradition that moderators serve one term only, and invite a former incumbent back for a second stint.
The Kirk has said the committee to nominate the moderator would now be recalled to bring forward the name of another minister to take over from current Moderator Right Reverend Lorna Hood..
While there is no precedent for a moderator-designate stepping down, the committee has wide-ranging powers to act in unforeseen circumstances.
Dr Morrison’s replacement is due to be announced on 2 April ahead of the opening of the Kirk’s General Assembly on 17 May. One Kirk insider last night said the decision could cause chaos for the Kirk’s preparations.
“I feel desperately sad for Angus and it’ll be a big loss for the church. I only hope and pray that we can get the right person in place for May,” he said. “The committee will need to look at other names and they’ll want to make sure they do the work properly but how it will happen in this timescale, nobody knows. It’s a nightmare for them.”
The moderator-designate is elected in October in order to allow complicated preparations for them taking up the role.
Dr Morrison had already stepped down as parish minister for the year to allow him to focus on preparing for the General Assembly.
The insider added: “They’re going to have to have somebody who is experienced, there’s just no doubt about that. This could be the year where a former moderator is invited back. This has never been talked about, but this time all bets are off.”