diff --git a/plugins/woocommerce-admin/TESTING-INSTRUCTIONS.md b/plugins/woocommerce-admin/TESTING-INSTRUCTIONS.md
index a74a2b43f72..ebfa21fefe6 100644
--- a/plugins/woocommerce-admin/TESTING-INSTRUCTIONS.md
+++ b/plugins/woocommerce-admin/TESTING-INSTRUCTIONS.md
@@ -2,6 +2,44 @@
 
 ## Unreleased
 
+### Add Guards to "Deactivate Plugin" Note Handlers #6532
+
+#### Test incompatible WooCommerce version
+
+-   Install and activate Woocommerce 4.7
+-   See that the Woocommerce Admin plugin is deactivated.
+-   Add the Deactivate Plugin note via SQL.
+
+```
+INSERT INTO `wp_wc_admin_notes` (`name`, `type`, `locale`, `title`, `content`, `content_data`, `status`, `source`, `date_created`, `date_reminder`, `is_snoozable`, `layout`, `image`, `is_deleted`, `icon`) VALUES ( 'wc-admin-deactivate-plugin', 'info', 'en_US', 'Deactivate old WooCommerce Admin version', 'Your current version of WooCommerce Admin is outdated and a newer version is included with WooCommerce.  We recommend deactivating the plugin and using the stable version included with WooCommerce.', '{}', 'unactioned', 'woocommerce-admin', '2021-03-08 01:26:44', NULL, 0, 'plain', '', 0, 'info');
+```
+
+-   See that the note is in the inbox
+-   Activate the Woocommerce Admin plugin.
+-   See that Woocommerce Admin immediately de-activates without a fatal error.
+-   See that the note remains in inbox
+
+#### Test compatible WooCommerce version
+
+-   Deactivate the Woocommerce Admin plugin.
+-   Install and activate the latest Woocommerce version.
+-   Add the Deactivate Plugin note via SQL.
+
+```
+INSERT INTO `wp_wc_admin_notes` (`name`, `type`, `locale`, `title`, `content`, `content_data`, `status`, `source`, `date_created`, `date_reminder`, `is_snoozable`, `layout`, `image`, `is_deleted`, `icon`) VALUES ( 'wc-admin-deactivate-plugin', 'info', 'en_US', 'Deactivate old WooCommerce Admin version', 'Your current version of WooCommerce Admin is outdated and a newer version is included with WooCommerce.  We recommend deactivating the plugin and using the stable version included with WooCommerce.', '{}', 'unactioned', 'woocommerce-admin', '2021-03-08 01:26:44', NULL, 0, 'plain', '', 0, 'info');
+```
+
+-   Activate the Woocommerce Admin plugin.
+-   See that note is **not** in the inbox
+-   Add the Deactivate Plugin note via SQL.
+
+```
+INSERT INTO `wp_wc_admin_notes` (`name`, `type`, `locale`, `title`, `content`, `content_data`, `status`, `source`, `date_created`, `date_reminder`, `is_snoozable`, `layout`, `image`, `is_deleted`, `icon`) VALUES ( 'wc-admin-deactivate-plugin', 'info', 'en_US', 'Deactivate old WooCommerce Admin version', 'Your current version of WooCommerce Admin is outdated and a newer version is included with WooCommerce.  We recommend deactivating the plugin and using the stable version included with WooCommerce.', '{}', 'unactioned', 'woocommerce-admin', '2021-03-08 01:26:44', NULL, 0, 'plain', '', 0, 'info');
+```
+
+-   De-activate the Woocommerce Admin plugin.
+-   See that note is **not** in the inbox
+
 ### Add legacy report items to new navigation #6507
 
 1. Enable the new navigation experience.
diff --git a/plugins/woocommerce-admin/readme.txt b/plugins/woocommerce-admin/readme.txt
index d645515b1ba..2c1ec328a9b 100644
--- a/plugins/woocommerce-admin/readme.txt
+++ b/plugins/woocommerce-admin/readme.txt
@@ -103,6 +103,7 @@ Release and roadmap notes are available on the [WooCommerce Developers Blog](htt
 - Fix: Associated Order Number for refunds was hidden #6428
 - Add: Remove Mollie promo note on install #6510
 - Add: Remote Inbox Notifications rule to trigger when WooCommerce Admin is upgraded. #6040
+- Fix: Add guard to "Deactivate Plugin" note handlers to prevent fatal error. #6532
 - Feature: Increase target audience for business feature step. #6508
 - Fix: Crash of Analytics > Settings page when Gutenberg is installed. #6540
 - Dev: Store profiler - Added MailPoet to Business Details step  #6503
diff --git a/plugins/woocommerce-admin/src/Composer/Package.php b/plugins/woocommerce-admin/src/Composer/Package.php
index 51c1d02709b..5c8487d4863 100644
--- a/plugins/woocommerce-admin/src/Composer/Package.php
+++ b/plugins/woocommerce-admin/src/Composer/Package.php
@@ -118,6 +118,10 @@ class Package {
 	 * Add deactivation hook for versions of the plugin that don't have the deactivation note.
 	 */
 	public static function on_deactivation() {
+		if ( ! self::is_notes_initialized() ) {
+			return;
+		}
+
 		$update_version = new DeactivatePlugin();
 		$update_version::delete_note();
 	}
@@ -127,6 +131,11 @@ class Package {
 	 * and adds/removes DeactivatePlugin note as necessary.
 	 */
 	public static function check_outdated_wca_plugin() {
+
+		if ( ! self::is_notes_initialized() ) {
+			return;
+		}
+
 		$update_version = new DeactivatePlugin();
 
 		if ( version_compare( WC_ADMIN_VERSION_NUMBER, self::VERSION, '<' ) ) {
@@ -137,4 +146,16 @@ class Package {
 			$update_version::delete_note();
 		}
 	}
+
+	/**
+	 * Checks if notes have been initialized.
+	 */
+	private static function is_notes_initialized() {
+		try {
+			\WC_Data_Store::load( 'admin-note' );
+		} catch ( \Exception $e ) {
+			return false;
+		}
+		return true;
+	}
 }