diff -u b/core/modules/mysql/src/Driver/Database/mysql/Connection.php b/core/modules/mysql/src/Driver/Database/mysql/Connection.php
--- b/core/modules/mysql/src/Driver/Database/mysql/Connection.php
+++ b/core/modules/mysql/src/Driver/Database/mysql/Connection.php
@@ -219,11 +219,22 @@
     // by one.
     $connection_options += [
       'init_commands' => [],
-        // @todo Switch to 'READ COMMITTED' for Drupal 10
-        //   see https://www.drupal.org/node/1650930.
-        'isolation_level' => 'REPEATABLE READ',
+      // @todo Switch to 'READ COMMITTED' for Drupal 10
+      //   see https://www.drupal.org/node/1650930.
+      'isolation_level' => 'REPEATABLE READ',
     ];
 
+    $isolation_levels = [
+      'READ COMMITTED',
+      'REPEATABLE READ',
+      'READ UNCOMMITTED',
+      'SERIALIZABLE',
+    ];
+
+    if (!in_array($connection_options['isolation_level'], $isolation_levels)) {
+      throw new DatabaseTransactionIsolationLevelException($connection_options['isolation_level']);
+    }
+
     $connection_options['init_commands'] += [
       'sql_mode' => "SET sql_mode = 'ANSI,TRADITIONAL'",
       'isolation' => 'SET SESSION TRANSACTION ISOLATION LEVEL ' . $connection_options['isolation_level'],
diff -u b/core/modules/mysql/tests/src/Functional/InstallerIsolationLevelExistingDatabaseSettingsTest.php b/core/modules/mysql/tests/src/Functional/InstallerIsolationLevelExistingDatabaseSettingsTest.php
--- b/core/modules/mysql/tests/src/Functional/InstallerIsolationLevelExistingDatabaseSettingsTest.php
+++ b/core/modules/mysql/tests/src/Functional/InstallerIsolationLevelExistingDatabaseSettingsTest.php
@@ -30,7 +30,7 @@
     }
 
     // Pre-configure database credentials in settings.php.
-    unset($connection_info['default']['pdo'], $connection_info['default']['init_commands']);
+    unset($connection_info['default']['pdo']);
 
     $this->settings['databases']['default'] = (object) [
       'value' => $connection_info,
@@ -46,7 +46,7 @@
     $contents = file_get_contents($this->container->getParameter('app.root') . '/' . $this->siteDirectory . '/settings.php');
 
     // Test that isolation_level were not override.
-    $this->assertStringNotContainsString("'isolation_level' => 'REPEATABLE READ',", $contents);
+    $this->assertStringNotContainsString("'isolation_level'", $contents);
 
     // Test that transaction level is REPEATABLE-READ.
     $this->assertEquals('REPEATABLE-READ', $database_connection->query('SELECT @@SESSION.transaction_isolation AS transaction_isolation')->fetch()->transaction_isolation);
diff -u b/sites/default/default.settings.php b/sites/default/default.settings.php
--- b/sites/default/default.settings.php
+++ b/sites/default/default.settings.php
@@ -138,11 +138,16 @@
  * request as needed.  The fourth line creates a new database with a name of
  * "extra".
  *
- * For MySQL users only, you can change the transaction isolation level using
- * 'isolation_level' setting. By default, MySQL will use 'READ COMMITTED'.
+ * For MySQL, MariaDB or equivalent databases can the option 'isolation_level'
+ * be set. The recommended option is 'READ COMMITTED'. Existing sites without
+ * this setting will default to 'REPEATABLE READ'. The other 2 options are
+ * 'READ UNCOMMITTED' and 'SERIALIZABLE'. They are available, but not supported.
+ * Use them at your own risk. For more info:
+ * https://dev.mysql.com/doc/refman/5.7/en/innodb-transaction-isolation-levels.html
  *
  * On your settings.php, change the isolation level:
  * @code
+ * $databases['default']['default']['isolation_level'] = 'READ COMMITTED';
  * $databases['default']['default']['isolation_level'] = 'REPEATABLE READ';
  * $databases['default']['default']['isolation_level'] = 'READ UNCOMMITTED';
  * $databases['default']['default']['isolation_level'] = 'SERIALIZABLE';
only in patch2:
unchanged:
--- a/core/assets/scaffold/files/default.settings.php
+++ b/core/assets/scaffold/files/default.settings.php
@@ -138,6 +138,21 @@
  * request as needed.  The fourth line creates a new database with a name of
  * "extra".
  *
+ * For MySQL, MariaDB or equivalent databases can the option 'isolation_level'
+ * be set. The recommended option is 'READ COMMITTED'. Existing sites without
+ * this setting will default to 'REPEATABLE READ'. The other 2 options are
+ * 'READ UNCOMMITTED' and 'SERIALIZABLE'. They are available, but not supported.
+ * Use them at your own risk. For more info:
+ * https://dev.mysql.com/doc/refman/5.7/en/innodb-transaction-isolation-levels.html
+ *
+ * On your settings.php, change the isolation level:
+ * @code
+ * $databases['default']['default']['isolation_level'] = 'READ COMMITTED';
+ * $databases['default']['default']['isolation_level'] = 'REPEATABLE READ';
+ * $databases['default']['default']['isolation_level'] = 'READ UNCOMMITTED';
+ * $databases['default']['default']['isolation_level'] = 'SERIALIZABLE';
+ * @endcode
+ *
  * You can optionally set a prefix for all database table names by using the
  * 'prefix' setting. If a prefix is specified, the table name will be prepended
  * with its value. Be sure to use valid database characters only, usually
only in patch2:
unchanged:
--- /dev/null
+++ b/core/modules/mysql/src/Driver/Database/mysql/DatabaseTransactionIsolationLevelException.php
@@ -0,0 +1,25 @@
+<?php
+
+namespace Drupal\mysql\Driver\Database\mysql;
+
+use Drupal\Core\Database\DatabaseException;
+
+/**
+ * Exception thrown if the isolation level is not valid.
+ *
+ * @see \Drupal\mysql\Driver\Database\mysql\Connection::open()
+ */
+class DatabaseTransactionIsolationLevelException extends \RuntimeException implements DatabaseException {
+
+  /**
+   * Constructs a DatabaseTransactionIsolationLevelException.
+   *
+   * @param string $isolation_level
+   *   The invalid isolation level.
+   */
+  public function __construct(string $isolation_level) {
+    $message = sprintf('The isolation level %s is not valid, use one of options available instead.', $isolation_level);
+    parent::__construct($message);
+  }
+
+}
only in patch2:
unchanged:
--- /dev/null
+++ b/core/modules/mysql/tests/src/Kernel/ConnectionTest.php
@@ -0,0 +1,39 @@
+<?php
+
+namespace Drupal\Tests\mysql\Kernel;
+
+use Drupal\Core\Database\Database;
+use Drupal\KernelTests\KernelTestBase;
+use Drupal\mysql\Driver\Database\mysql\Connection;
+use Drupal\mysql\Driver\Database\mysql\DatabaseTransactionIsolationLevelException;
+
+/**
+ * Tests the connection class.
+ *
+ * @coversDefaultClass \Drupal\mysql\Driver\Database\mysql\Connection
+ *
+ * @group Mysql
+ */
+class ConnectionTest extends KernelTestBase {
+
+  /**
+   * Tests transaction isolation level when an invalid option is set.
+   *
+   * @covers ::open
+   */
+  public function testInvalidIsolationLevelOption() {
+    $connection_info = Database::getConnectionInfo();
+
+    // The isolation_level option is only available for MySQL.
+    if ($connection_info['default']['driver'] !== 'mysql') {
+      $this->markTestSkipped("This test does not support the {$connection_info['default']['driver']} database driver.");
+    }
+
+    $connection_info['default']['isolation_level'] = 'INVALID_LEVEL';
+    $this->expectException(DatabaseTransactionIsolationLevelException::class);
+    $this->expectExceptionMessage("The isolation level INVALID_LEVEL is not valid, use one of options available instead.");
+
+    Connection::open($connection_info['default']);
+  }
+
+}