Executive Summary:
When you're configuring a new Microsoft Windows server that has multiple network interface cards (NICs), it's important that you disable any NICs that aren't plugged in to the network. If you don't disable an unused NIC, problems can arise on domain controllers (DCs) running Domain Name System (DNS). The DNS server problems can impede the performance of client computers.

When you're configuring a new server that has multiple NICs, it's important that you disable any NICs that aren't plugged in to the network. If you don't disable an unused NIC, the Windows software will assign it an IP address from the 169.254.x.x subnet. This address isn't used anywhere on the network and isn't routable across any WAN routers.

At this point you might be thinking, "So if it isn't connected, what's the problem?" Problems can arise on domain controllers (DCs) running DNS. Servers register all active IP addresses with the default DNS server. On a DC, this has the side effect of registering the server in Active Directory (AD) as a DC with two IP addresses: its valid IP address and the invalid 169.254.x.x address.

When a client makes a DNS request to find all the DCs for the appropriate domain, occasionally the client will be given the invalid 169.254.x.x address as a valid DC address because addresses are returned in a round-robin fashion. The client will then attempt to contact the DC using this invalid address. Of course, it won't be able to contact the DC, and the connection will fail. The client will then attempt to look up another DC using DNS. Eventually the client will succeed, and all will be fine. However, all these extra lookups will slow down the client computer.

We learned about this problem while attempting to connect a new storage appliance. The appliance was able to register with the domain but periodically would be unavailable when we attempted to browse for files located on the appliance. We had to manually go through DNS and remove all of the invalid entries and reregister the appliance with the domain to correct the problem.

So, the moral of the story is this: If you have multiple NICs in a server, disable those NICs that aren't being used.
—Chris Lamb, Director, IT Infrastructure, HIT Entertainment