I'm downloading Pyramid of Shadows now.
Is there anything in particular that triggers this? One person in the comments of Pyramid of Shadows mentioned it started after a crash.
Try browsing to the '..\Documents\Larian Studios\Divinity Original Sin 2 Definitive Edition\LevelCache' folder and delete the contents. A corrupt file there can cause problems when saving or loading.
Try exiting out of the Steam client, and starting the game directly from the '..\SteamApps\common\Divinity Original Sin 2\DefEd\bin\EoCApp.exe' program file, by right clicking and running as administrator.
If you create a new profile and start a new game, can you save and load properly? How long does it generally take to run into this problem (if you've gotten multiple reports, or started multiple playthroughs when testing)?
Please email supportdos2@larian.com with a Pyramid of Shadows save (or email/PM/post a Dropbox or Google drive link, etc), and if older saves are ok, the most recent save that you can load, and the oldest you can not. If you are using any non-Larian mods, also include a list of those enabled and/or the modsettings.lsx file from your profile folder.