diff --git a/lib/externallib.php b/lib/externallib.php
index 8358fc21204..b17375c43cf 100644
--- a/lib/externallib.php
+++ b/lib/externallib.php
@@ -24,10 +24,16 @@
 
 use core_external\util;
 
+defined('MOODLE_INTERNAL') || die;
+
 // Please note that this file and all of the classes and functions listed below will be deprecated from Moodle 4.6.
 // This deprecation is delayed to aid plugin developers when maintaining plugins for multiple Moodle versions.
 // See MDL-76583 for further information.
 
+// If including this file for unit testing, it _must_ be run in an isolated process to prevent
+// any side effect upon other tests.
+require_phpunit_isolation();
+
 class_alias(\core_external\external_api::class, 'external_api');
 class_alias(\core_external\restricted_context_exception::class, 'restricted_context_exception');
 class_alias(\core_external\external_description::class, 'external_description');
diff --git a/lib/phpunit/classes/advanced_testcase.php b/lib/phpunit/classes/advanced_testcase.php
index 048e04d420c..7e413cacf02 100644
--- a/lib/phpunit/classes/advanced_testcase.php
+++ b/lib/phpunit/classes/advanced_testcase.php
@@ -57,6 +57,20 @@ abstract class advanced_testcase extends base_testcase {
         $this->setBackupGlobals(false);
         $this->setBackupStaticAttributes(false);
         $this->setPreserveGlobalState(false);
+
+    }
+
+    /**
+     * Hook into the setInIsolation method to define an optional constant.
+     *
+     * @param bool $inisolation
+     */
+    public function setInIsolation(bool $inisolation): void {
+        parent::setInIsolation($inisolation);
+        if ($inisolation) {
+            // Note: This is safe to do because it will only be set once per test run.
+            define('PHPUNIT_ISOLATED_TEST', true);
+        }
     }
 
     /**
diff --git a/lib/setuplib.php b/lib/setuplib.php
index 58a946b6cff..d87dc9dd457 100644
--- a/lib/setuplib.php
+++ b/lib/setuplib.php
@@ -2183,3 +2183,26 @@ function proxy_log_callback($code) {
         error_log($error . format_backtrace($trace, true)); // phpcs:ignore
     }
 }
+
+/**
+ * A helper function for deprecated files to use to ensure that, when they are included for unit tests,
+ * they are run in an isolated process.
+ *
+ * @throws \coding_exception The exception thrown when the process is not isolated.
+ */
+function require_phpunit_isolation(): void {
+    if (!defined('PHPUNIT_TEST') || !PHPUNIT_TEST) {
+        // Not a test.
+        return;
+    }
+
+    if (defined('PHPUNIT_ISOLATED_TEST')) {
+        // Already isolated.
+        return;
+    }
+
+    throw new \coding_exception(
+        'When including this file for a unit test, the test must be run in an isolated process. ' .
+            'See the PHPUnit @runInSeparateProcess and @runTestsInSeparateProcesses annotations.'
+    );
+}
diff --git a/lib/tests/setuplib_test.php b/lib/tests/setuplib_test.php
index d2c65355291..2b25604b45b 100644
--- a/lib/tests/setuplib_test.php
+++ b/lib/tests/setuplib_test.php
@@ -520,4 +520,26 @@ class setuplib_test extends \advanced_testcase {
         $uuid = \core\uuid::generate();
         $this->assertTrue(self::is_valid_uuid_v4($uuid), "Invalid v4 UUID: '$uuid'");
     }
+
+    /**
+     * Test require_phpunit_isolation in a test which is not isolated.
+     *
+     * @covers ::require_phpunit_isolation
+     */
+    public function test_require_phpunit_isolation(): void {
+        // A unit test which is not isolated will throw a coding_exception when the function is called.
+        $this->expectException('coding_exception');
+        require_phpunit_isolation();
+    }
+
+    /**
+     * Test require_phpunit_isolation in a test which is isolated.
+     *
+     * @covers ::require_phpunit_isolation
+     * @runInSeparateProcess
+     */
+    public function test_require_phpunit_isolation_isolated(): void {
+        $this->expectNotToPerformAssertions();
+        require_phpunit_isolation();
+    }
 }