I use Wrye Bash to handle flagging/unflagging .esm and .esp on the plugins and parenting other .esp to a master file. I know its not common, but for some mods it is useful, and when I parent an .esp to another .esp instead of to an .esm, when I save in the Construction Set, the relationship to the master file is lost, and I have to re-apply the master to the file in Wrye Bash before loading the game or running the CS again or all edits are lost/crash.

Is there a way to make it so that the master relationship is not lost when the file is saved when the master is an esp?

Just use CSE, it will handle all the de-isolation for you.

Not being a serious modder (modding other people's mods to shoehorn them all together how I like it so I can't really "release" anything I do) I somehow did not know that this existed. A quick google of "CSE Oblivion" and suddenly many things are a lot less of a pain in the CS! Thank you much and thank you to the authors of CSE. Isolation on save is not a problem anymore for one.

Search for Construction Set Extender in the mods forum. You'll get the info about it and download links.