The veteran leader, who is battling to form a new government to salvage her political future, warned it would be a "tough day" of talks, which were expected to stretch well into the night.
She said her conservative Christian Democrats would "work constructively to find the necessary compromises but we are also aware that we need to execute the right policies for our country".
September's inconclusive elections left Merkel without a majority and struggling to find partners to govern Europe's biggest economy.
SPD leader Martin Schulz also spoke of "big obstacles" on the last day of preliminary talks in which the parties were sounding each other out over whether to move on to formal coalition negotiations.
He said his party wanted to ensure that the new government committed "above all to working toward renewal of the European Union".
President Frank-Walter Steinmeier reminded all sides that they "have a responsibility towards Europe and for reliability, partnership and engagement in international politics".
"The negotiations are not just about a coalition, but also their careers. It would be the end for all three if this coalition does not come about," he told public broadcaster ZDF.
The parties are due to declare whether they will push on with efforts to forge a new government by around March or April.
Along the way, negotiators need to compromise on policy differences -- the SPD is seeking welfare gains while the conservatives are pushing for tax cuts as Germany's public coffers bulge.
Beyond fiscal and spending issues, the parties are struggling to fend off the encroaching far right, which has seized on anger over the influx of refugees and netted a record showing at the polls in September.
To halt a haemorrhage to the far right, Merkel's alliance wants a tougher stance on immigration, something that is hard to sell to the centre-left SPD.
SPD vice chairman Ralf Stegner underlined the deep uncertainty about a possible deal, tweeting that "scepticism was, is and remains justified", while the party's Karl Lauterbach said the "negotiations are difficult ... in all areas".
The SPD's youth wing chief Kevin Kuehnert is also energetically running a resistance campaign against any grand coalition agreement with the conservatives, known as a "GroKo" in German.
He told Zeit Online that he would embark on a #NoGroKo national tour to press his case before a September 21 party congress.
The SPD's youth movement leader believes that governing for another four years under Merkel would deal a death blow to the Social Democrats, who suffered a historic low score in September's elections.
Instead, Kuehnert favours a minority government led by Merkel, even though her conservatives have rejected that option as too unstable.
A survey published by Focus magazine found that only 30 per cent of Germans favour a return of the conservative-SPD alliance, while 34 per cent prefer new elections.
And a third survey, for business paper Handelsblatt, showed that 56 per cent believed Merkel would not see out her four-year term.
Disclaimer: No Business Standard Journalist was involved in creation of this content
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