In his first response to the vote that signals a new dawn for both the UK and EU, European Parliament President Martin Schulz said he would speak with German Chancellor Angela Merkel "on how we can avoid a chain reaction" of other EU states following the UK's exit path.
"The chain reaction that is being celebrated everywhere now by eurosceptics won't happen," he said, adding, that the UK had now "cut its ties" to the biggest single market in the world.
Amid fast moving political developments to the result, Schulz said he expected negotiations over Britain's departure to start soon, saying, "The United Kingdom has decided to go its own way. I think the economic data show this morning that it will be a very difficult way."
“I expect that negotiations on the exit will now begin quickly," he said, noting a fall in Sterling after the referendum result became clear. "I don't want the euro to experience something similar.”
Scottish First Minister Nicola Sturgeon moved quickly to announce that a second Scots referendum on independence was now “very likely.”
Her comments came after every voting area in Scotland backed remaining in the EU in contrast to much of England.
Sturgeon said “all options will be explored” in the coming days and weeks and that a second referendum, probably within the next two years, was the "best and only way to protect" Scotland's interests.
European Commission President Jean-Claude Juncker said, "In a free and democratic process, the British people have expressed their wish to leave the European Union. We regret this decision but respect it."
“This is an unprecedented situation but we are united in our response. We will stand strong and uphold the EU's core values of promoting peace and the well-being of its peoples. The Union of 27 Member States will continue. The Union is the framework of our common political future. We are bound together by history, geography and common interests and will develop our cooperation on this basis."
“Together we will address our common challenges to generate growth, increase prosperity and ensure a safe and secure environment for our citizens. The institutions will play their full role in this endeavour.”
Further comment came from French President Francois Hollande who called the result a “sad choice” while German Chancellor Angela Merkel, speaking in Berlin, expressed “great regret.”
Merkel said, “Let us not forget the reason why the EU is based on peace after centuries of bloodbath and violence. This is not something we can take for granted.”
“It is important that we stay calm and composed. The EU is strong enough to give the right responses today and I will work for that.”
She said she would have talks with other EU leaders on the result next Week in Brussels.
On Tuesday, the European Parliament will hold an extraordinary plenary session to assess the outcome. All the parliament's planned committee meetings for the Monday have been cancelled to allow MEPs to prepare for the special gathering.
Leader of the parliament's largest political grouping, EPP chairman Manfred Weber, who will lead the debate, said that Britain's exit negotiations “should be swiftly concluded, within the two-year deadline, as defined in the Lisbon Treaty, respecting the democratic decision of the British voters.”
Weber added that, “there cannot be any special treatment for the United Kingdom. The British people have expressed their wish to leave the EU. Leave means leave".
Foreign ministers from the six founding members of the EU including Belgium, will also meet in Berlin on Saturday to discuss the outcome.
Meanwhile, the Kremlin has issued a statement saying Russia “hopes the UK will understand the need for better relations” with Moscow.
The mayor of Moscow told Russian media that he believes the decision will now lead to an erosion of EU support for sanctions against Russia in wake of the conflict in Ukraine.