Do I always have to refresh my Picklist manually?

No, although at any time you have the ability to manually refresh a Picklist by clicking on the Retrieve Values button on the Picklist's Overview page, you additionally have the ability to define Auto Refresh settings for it. You can choose a day/days of the week and an hour of the day that your Picklist will be automatically refreshed.

Note: Starting in December 2025, all values that have been removed from a DE are automatically removed from the respective Picklist. All newly created Picklists (created after December 2025) are automatically subject to this policy.

For Picklists created before December 2025, you need to activate the “Remove Missing Values” toggle in the Admin Panel. To do so:

• Navigate to the Admin Panel > Picklists.

• Press the "gear" Icon.

• Toggle on  "Remove Missing Values".
  

More details on how this functionality works can be found below: 

• DESelect November ’20 Release: Auto refresh picklist values, and relations on multiple fields