"If the goal is regime change, it sure doesn't seem to be working and probably it punishes the people more than the regime because the regime can blame the embargo for hardship," he said.
Potential challengers, Jeb Bush and Sen. Marco Rubio, both of Florida, denounced President Barack Obama's decision to open diplomatic and economic ties with Cuba. Sen. Ted Cruz of Texas also slammed the deal.
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Bush called it a "misstep" that "undermines America's credibility and undermines the quest for a free and democratic Cuba."
And Rubio, the son of Cuban immigrants, vowed to use his role as incoming chairman of a Foreign Relations subcommittee to block progress on policy.
"The White House has conceded everything," Rubio said, calling the policy "disgraceful."
Paul, who has often bumps heads with members of his party over foreign policy, expressed a similar position to another potential presidential candidate, Hillary Clinton.
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"Despite good intentions, our decades-long policy of isolation has only strengthened the Castro regime's grip on power," Clinton said in a statement. "As I have said, the best way to bring change to Cuba is to expose its people to the values, information, and material comforts of the outside world."