Sheriffs still have to fallow the law. It would not be as easy as falling off a log, but it would not be that hard either.
They swear to uphold the Constitution, and the laws of the State they are Sheriff's in. If a Fed law is unconstitutional, or even if a state law is a violation of the Constitution, at the Sheriff's discretion, as the highest ranking LE Officer in that jurisdiction, the Sheriff can and is obligated to tell them to pound sand!!!
Review the post here regarding the cutting down of trees on Federal land out west to fight a wildfire. The Feds threatened action against anyone cutting down trees on Fed Land, regardless of why.
The Sheriff and the House Representative from Congress showed up with a tree cutting crew and local firefighters, the FED showed up and the Sheriff threatened to arrest them for interfering with a local matter.
The Feds left.