diff --git a/core/modules/system/system.install b/core/modules/system/system.install
index cfa0966abbc8..15b4f4858774 100644
--- a/core/modules/system/system.install
+++ b/core/modules/system/system.install
@@ -316,6 +316,19 @@ function system_requirements($phase) {
   elseif ($phase === 'runtime' && version_compare($phpversion, \Drupal::RECOMMENDED_PHP) < 0) {
     $requirements['php']['description'] = t('It is recommended to upgrade to PHP version %recommended or higher for the best ongoing support.  See <a href="http://php.net/supported-versions.php">PHP\'s version support documentation</a> and the <a href=":php_requirements">Drupal PHP requirements</a> page for more information.', ['%recommended' => \Drupal::RECOMMENDED_PHP, ':php_requirements' => 'https://www.drupal.org/docs/system-requirements/php-requirements']);
     $requirements['php']['severity'] = REQUIREMENT_INFO;
+
+    // PHP 8.1.0 through 8.1.5 have a known OPcache bug that can cause fatal
+    // errors, so warn about that when running Drupal on those versions.
+    // @todo Remove this when \Drupal::MINIMUM_PHP is at least 8.1.6 in
+    //   https://www.drupal.org/i/3305726.
+    if (version_compare(\Drupal::MINIMUM_PHP, '8.1.6') < 0) {
+      $requirements['php']['description'] = t('PHP %version has <a href=":bug_url">an OPcache bug that can cause fatal errors with class autoloading</a>. This can be fixed by upgrading to PHP 8.1.6 or later. See <a href="http://php.net/supported-versions.php">PHP\'s version support documentation</a> and the <a href=":php_requirements">Drupal PHP requirements</a> page for more information.', [
+        '%version' => $phpversion,
+        ':bug_url' => 'https://github.com/php/php-src/issues/8164',
+        ':php_requirements' => 'https://www.drupal.org/docs/system-requirements/php-requirements',
+      ]);
+      $requirements['php']['severity'] = REQUIREMENT_WARNING;
+    }
   }
 
   // Test for PHP extensions.
diff --git a/core/modules/system/tests/src/Functional/System/PhpRequirementTest.php b/core/modules/system/tests/src/Functional/System/PhpRequirementTest.php
index dfb63bee495b..905087ffc24a 100644
--- a/core/modules/system/tests/src/Functional/System/PhpRequirementTest.php
+++ b/core/modules/system/tests/src/Functional/System/PhpRequirementTest.php
@@ -72,7 +72,17 @@ class PhpRequirementTest extends BrowserTestBase {
     // There should be an informational message if the PHP version is below the
     // recommended version.
     if (version_compare($phpversion, \Drupal::RECOMMENDED_PHP) < 0) {
-      $this->assertSession()->pageTextContains('It is recommended to upgrade to PHP version ' . \Drupal::RECOMMENDED_PHP . ' or higher');
+      // If it's possible to run Drupal on PHP 8.1.0 to 8.1.5, warn about a
+      // bug in OPcache.
+      // @todo Remove this when \Drupal::MINIMUM_PHP is at least 8.1.6 in
+      //   https://www.drupal.org/i/3305726.
+      if (version_compare(\Drupal::MINIMUM_PHP, '8.1.6') < 0) {
+        $this->assertSession()->pageTextContains("PHP $phpversion has an OPcache bug that can cause fatal errors with class autoloading. This can be fixed by upgrading to PHP 8.1.6 or later.");
+        $this->assertSession()->linkExists('an OPcache bug that can cause fatal errors with class autoloading');
+      }
+      else {
+        $this->assertSession()->pageTextContains('It is recommended to upgrade to PHP version ' . \Drupal::RECOMMENDED_PHP . ' or higher');
+      }
     }
     // Otherwise, the message should not be there.
     else {