Speaking during a tour of Eastern European nations, Biden urged European allies to use their influence and "promote a stable and positive environment" so Ukrainians can vote unhindered on Sunday.
"If Russia undermines these elections ... we must remain resolute and impose greater costs to Russia and (be) equally resolute to invest in the NATO alliance," Biden said after talks with Romanian President Traian Basescu.
The U.S. and the EU have imposed travel bans and asset freezes on President Vladimir Putin's inner circle over Russia's annexation of Crimea and have threatened to target entire sectors of the Russian economy if Russia tries to grab more land from Ukraine.
Biden urged Romania to develop its natural gas resources, which analysts say could be exported it to other countries in the region, including neighboring Moldova, which is 100 percent dependent on Russian gas.
Romania imports about one-fifth of its natural gas from Russia and has its own supplies in the northwest Transylvania region.
"We need to ensure that Russia can no longer use its energy resources as a weapon against anyone in the region," Biden said. "The development of a secure, diverse and inter-connected energy market is the next great step for our European colleagues."
He sought to reassure Romania that it would be protected by NATO if it were attacked.
"NATO nations never stand alone, we protect one another," he said.
Biden said an U.S. anti-missile shield at Romania's Deveselu site was on track to become operational in 2015 and praised Bucharest's plans to increase defense spending to two percent of GDP by 2016, up from about 1.5 percent.
The U.S. has said the missile interceptors could be launched from Romania in case of a missile attack from the Middle East.