"We know that if they give an excuse to the EU, there are at least five countries right now that want to say 'We want out'" of sanctions against Moscow, Biden said, speaking to the Council on Foreign Relations in New York, Reuters reported.
Europe imposed sanctions after Russia annexed Ukraine's Crimea peninsula in 2014. Fighting has continued in the east of the country, despite the so-called Minsk ceasefire agreement, and Western powers fear peace efforts could unravel.
Read alsoEU prolongs for 6 mths sanctions over violation of Ukraine's sovereigntyIn exchange for financial support from the United States and other Western allies, Ukraine promised reforms, but progress has been mixed.
Biden's comments came a day after he met with Ukrainian President Petro Poroshenko at the United Nations, pushing on reforms in Ukraine's energy and justice sectors, while saying conditions had been met for a third U.S. sovereign loan guarantee of up to $1 billion.
Read alsoBiden to Poroshenko: Steps taken to go ahead with $1 bln loan guaranteeBiden said he has spent two to three hours a week on the phone with Ukrainian leaders since the crisis began, urging them to persist with reforms, while also pressuring Germany, France and Italy to hold fast on sanctions.
"There's an overwhelming instinct in Europe to say, 'Hey: before [Poroshenko] became president, this was owned by Russia anyway. They had a puppet there. What difference does it make? What the hell's the difference? Why are you making us engage in these sanctions?'" Biden said.
Noting a crisis of "self-doubt" in Europe caused by the United Kingdom's referendum decision to leave the bloc and the Syrian migration crisis, Biden said he has warned Poroshenko to make sure that the failure of the Minsk deal is not blamed on Ukraine.
Read alsoDisengagement of forces in Donbas to start only after seven days of "full silence" - Framework Decision"I've been the guy on the back of Ukrainians - which was a thoroughly corrupt system when they came in - making the case that, 'You have to understand: everybody's willing to blame the victim, and you better straighten up and fly right,'" Biden said.