Koehler's surprise resignation created another headache for the already under-pressure Merkel, 55, whose popularity has plummeted barely half a year into her second term.
"I tried to get the president to change his mind but unfortunately I was unsuccessful," Merkel told reporters.
"I always worked very well together with Horst Koehler. He was an important adviser, particularly in the financial and economic crisis, with his large international experience.
"I will miss this advice."
A former head of the International Monetary Fund, the popular Koehler, a political ally of the conservative Merkel, was elected by MPs in 2004 and won a second term only a year ago.
But he came under fire earlier this month for saying that an export-reliant country like Germany occasionally needed to defend its economic interests.
Regional instabilities "certainly have a negative impact on us through trade, jobs and income," Koehler told German radio on May 22.
After the interview, Koehler said his comments were "misunderstood" and that they were not meant to refer to the mission in Afghanistan, where Germany has around 4,350 troops in a NATO-led force tackling a Taliban-led insurgency.
"It is not the president's job to get mixed up in political affairs but he did. He should not be surprised that the criticism was so severe," Wichard Woyke from the University of Muenster told television station NTV.
His departure came less than a week after Roland Koch, a one-time rival to Merkel but a big hitter in conservative bloc, resigned as premier of the state of Hesse, home to Germany's banking capital Frankfurt.
"She has lost Koch, she is losing Koehler, who is not very important in terms of political power, but it is symbolic and it could create some panic," political scientist Nils Diederich from Berlin's Free University told AFP.
"If she doesn't manage to get a grip on her political agenda in the coming weeks she is not going to serve out her full term."
Under the constitution, the speaker of Germany's upper house, the Bundesrat, currently Jens Boehrnsen from the opposition Social Democrats, takes over Koehler's duties provisionally. A successor must be named within 30 days.
Merkel's squabbling coalition now has to agree on a candidate.
Sigmar Gabriel, head of the opposition Social Democrats, which opposed Koehler's re-election, said he also regretted his departure but that he suspected there was more to it than just his comments on Afghanistan.
"I really can't see a good reason for his departure, other than the fact that Horst Koehler obviously had the impression that those who brought him into office didn't give him enough support," Gabriel told reporters.
Merkel, as is her usual style, declined last week to talk about Koehler's comments about military operations, and her spokeswoman insisted that the government was barred by the constitution from commenting on the president.
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