It does persist the setting (but I don't know where). So your $PATH will be preserved across restarts of the shell.

It's used in the [fish tutorial](http://fishshell.com/docs/current/tutorial.html#tut_startup) (scroll very slightly up). And here is what the `set` man page says for the `-U` option:

>  -U or --universal causes the specified environment variable to be given a universal scope. If this option is supplied, the variable will be shared between all the current users fish instances on the current computer, and will be preserved across restarts of the shell.