[Pollster1]

I would argue that a federal agent acting outside the Enumerated Powers can lawfully be resisted by a local sheriff. In fact, the Bill of Rights makes this clear:

"The enumeration in the Constitution, of certain rights, shall not be construed to deny or disparage others retained by the people."

and

"The powers not delegated to the United States by the Constitution, nor prohibited by it to the States, are reserved to the States respectively, or to the people."

[Tarheel25]

Not exactly. The judicial system is the proper and lawful venue for challenging federal laws that might run afoul of the powers delegated to the federal government in the US Constitution. If any sheriff could just hypothetically disagree and nullify a a federal law in their county then you would have hundreds and hundreds of different interpretations which would lead to mass confusion and instability. A sheriff just like any other regular civilian is subject to obey federal laws. Even the state governor has to obey federal law.