In rare cases, you may not be able to enable the SpamSieve plug-in in Mail because the plug-in is not listed in the Manage Plug-ins… sheet. Or you may click the checkbox to enable it, but it will not stay enabled when you restart Mail.
First, try to uninstall and reinstall the plug-in. Choose Uninstall Plug-In… in Settings ‣ Apple Mail ‣ Setup, restart Mail, and then choose Install Plug-In in Settings ‣ Apple Mail ‣ Setup. Mail maintains its own separate copy of installed plug-ins, and restarting after uninstalling can get it to clear out its damaged copy, whereas simply installing a fresh copy of the plug-in will not. You may want to temporarily uncheck your SpamSieve rules in Mail’s settings before doing this, so that the uninstaller doesn’t offer to delete them, and so that Mail doesn’t move any messages to the Junk mailbox while the plug-in is uninstalled.
If that doesn’t help, make sure that you have not redirected Mail’s plug-ins folder to be stored in a different location. If you haven’t tried to move Mail’s files or your home folder, you can skip this step. The folder:
/Users/<username>/Library/Mail/Bundles
must be stored on the same volume as your home folder (and, ideally, on the boot volume) or Mail will not trust its contents. So you should not try to redirect the whole Mail folder to another location, e.g. using a symlink. If you really want your mail to be stored on a different volume, you can move just the V10 or V9 folder and replace it with a symlink, or use the Users & Groups settings pane to move your entire home folder to a different volume.
If you still can’t enable the plug-in, or if Mail reports “Incompatible Plug-ins Disabled,” the problem may be that Mail’s private plug-ins folder is damaged and needs to be reset. Please see the instructions in Resetting Mail’s Private Plug-Ins Folder.