"The EU will examine the implications of this initiative on EU-Swiss relations as a whole," the commission said in a statement after Swiss results showed a narrow victory for a proposal pushed by right-wing populists.
The European Commission said it "regrets" the Swiss vote, which "goes against the principle of free movement of persons between the EU and Switzerland."
Although Switzerland is not an EU member, it signed onto the EU accord for free movement of citizens in 1999 and implemented it from 2007.
While Sunday's vote focused only on that issue, fall-out from the result could imperil Switzerland's trade with the big European bloc, which its economy depends on.
Brussels has already made it clear that Bern cannot cherry-pick among EU advantages.
An estimated 400,000 Swiss citizens live in the EU, many of them dual nationals, while more than a million EU citizens currently live in Switzerland.
Wolfgang Schäuble, finance minister of Germany, Switzerland's top trade partner, said the result "is going to create plenty of problems for Switzerland in a host of areas".
But he said it was also a warning sign of European globalization fears.
Swiss President and Foreign Affairs Minister Didier Burkhalter said he planned to tour European capitals to explain the vote and seek a solution, starting with Berlin.
"The people are sovereign, and a healthy system doesn't force the public to follow political authorities with outsized powers," Burkhalter said.
The Swiss government and a broad swathe of economic lobby groups fearing the EU fall-out had battled the immigration curb plan.
But under Switzerland's system of direct democracy, voters have the last word on a huge range of issues.
The leader of Britain's main eurosceptic party on Sunday hailed "wise" Swiss voters for backing curbs on EU immigration, saying it would encourage others across the continent.
Nigel Farage, the head of the UK Independence Party, said Switzerland had stood up to "bullying" from Brussels and that it was "not a matter of race but of space."
"This is wonderful news for national sovereignty and freedom lovers throughout Europe," said Farage, who is a member of the European parliament (MEP).
"A wise and strong Switzerland has stood up to the bullying and threats of the unelected bureaucrats of Brussels."
UKIP has led calls for similar calls for a cap on immigration, a touchy issue in Britain since Bulgarians and Romanians were given full rights on January 1st to free movement within the EU.
Farage added: "It is a great thing to be welcomed that the Swiss people now have the freedom to decide the number and skill level of the people who they wish to invite to work or stay in their country."
UKIP has no lawmakers in the British parliament but threatens to sap vital votes from Prime Minister David Cameron's Conservative party in Britain's next general election in May 2015.
It is also hoping to expand its total of nine MEPs in European elections this May.
Under pressure from UKIP and eurosceptic Conservatives, Cameron has promised a referendum on membership of the EU in 2017, provided that he is re-elected next year.