What settings won't save? Changes should take effect immediately. If they don't restart TB. If the problem persists, see if still happens in [Troubleshoot mode](https://support.mozilla.org/en-US/kb/safe-mode-thunderbird).

I no longer wish to use two email accounts set up in TB. I have gone into Account Settings/Server Settings for each of the two accounts then unticked Server Settings/Check for new messages at Startup, Check for new messages every 10 minutes and Automatically download new messages. In addition I have set a third account now to set as default using the Account Actions tab. There is no option to confirm or cancel the changes. These changes remain current whilst within TB but disappear once TB is closed. I have attempted to make these cahnges numerous times including under safe mode.

Short fix: remove the two accounts you don't want to use.

Long possible fix: create a [new profile](https://support.mozilla.org/en-US/kb/profile-manager-create-and-remove-thunderbird-profiles).