If there is a search warrant, I would say they can ask you to open the safe or take the safe until they can open it. I would be surprised to find that by putting something in a safe, you can prevent the police from carrying out a lawful court order.
Some difference in opinion on that. One court has ruled that they can make you provide a physical key to a lockbox but there is some dispute over whether a court can compel you to provide a memorized combination.
http://blogs.denverpost.com/crime/2012/01/05/why-criminals-should-always-use-combination-safes/3343/
Personally, I don’t think the distinction between a combination and a key will stand. I also believe that the courts will rule that you can be compelled to unlock your electronic records through a court order. You won’t be compelled to identify what the records are or why they might or might not be relevant but you would have to provide access.
I would be surprised if you could stop them even if they don't have a court order. All they have to do is cry terrorist.