Does the hard disk sleep setting in Energy Saver affect drives in the optical drive bay? If a second hard drive is mounted in the optical drive bay of a MacBook Pro, will it be affected by the Energy Saver setting for "Put the hard disk(s) to sleep when possible"?

If it is affected, is there a way I can instruct the OS to sleep one drive, but not the other?
Yes it does. The OWC blog talks about this and shows a terminal tip to set spin-down time to a shorter delay, saving a bit more power. 

When you think about it the disk is still on the SATA bus - no reason it shouldn't spin down. I don't think you can address each drive individually though.

A cumbersome solution is to eject the disk when you no longer need it. But then you can't unplug/replug it like you would for an external drive. To remount it, in terminal you would do:

diskutil list

diskutil mountDisk /dev/disk1


I experimented with my Time Machine drive to see if this works. Your optical bay drive may well be /dev/disk1, but that's why you did diskutil list - to see what its identifier is.

(Rebooting will remount the drive too, if you forget the diskutil command)