I'm having an extremely frustrating problem with my UI; the size resets upon restarting the engine. I have it set up as follows:
CenterContainer
-> VBoxContainer
-> menu item 1 (TextureButton)
-> menu item 2 (TextureButton)
-> menu item 3 (TextureButton)

Both containers' size flags are set to 'Horizontal: fill, expand' and 'Vertical: fill, expand'. I had this exact issue before too, and setting the flags to the aforementioned settings worked. That was before adding the parent CenterContainer, though.
Not sure if worth mentioning, but the above nodes reside in another VBoxContainer, also set to 'fill, expand'.