On Mac OS X El Capitan (10.11.4), I was trying to change the default email reader to MS Outlook. So I went to Mail > Preferences > General, and changed Default email reader to Outlook. However, if I re-open the Preferences dialog, I noticed the setting is reverted back to Mail.
I was able to resolve the issue by resetting LaunchServices. Open Terminal and run the following command:
/System/Library/Frameworks/CoreServices.framework/Versions/A/Frameworks/LaunchServices.framework/Versions/A/Support/lsregister -kill -seed
OS X 10.11.4 - Setting the default email to one... | Apple Support Communities