diff -u b/includes/bootstrap.inc b/includes/bootstrap.inc
--- b/includes/bootstrap.inc
+++ b/includes/bootstrap.inc
@@ -899,9 +899,15 @@
         $missing = array();
         try {
           if (function_exists('cache_get')) {
-            $cache = cache_get('drupal_get_filename:missing');
+            $cache = cache_get('drupal_get_filename:missing', 'cache_bootstrap');
             if (!empty($cache->data)) {
-              $missing = $cache->data;
+              // Merge the changes already done in the current request (including
+              // the setting of missing records to NULL) into the values saved
+              // in persistent cache.
+              $missing = $cache->data + $missing;
+              // Set a flag so we know that we've already done a merge with values
+              // in cache_get().
+              $missing['#cache_merge_done'] = TRUE;
             }
           }
         }
@@ -917,7 +923,7 @@
         }
         else {
           // File is not available anymore at its new location. Re-do file scan.
-          unset($missing[$type][$name]);
+          $missing[$type][$name] = NULL;
           $missing['#write_cache'] = TRUE;
         }
       }
@@ -957,7 +963,7 @@
     if (!isset($missing[$type][$name])) {
       // Add the missing file to a temporary cache and throw an alert.
       // This cache will be cleared on module/theme rebuild.
-      $missing[$type][$name] = FALSE;
+      $missing[$type][$name] = TRUE;
       $missing['#write_cache'] = TRUE;
     }
     trigger_error(format_string('The following @type is missing from the file system: @name. For more information, see <a href="@documentation">the documentation page</a>.', array('@type' => $type, '@name' => $name, '@documentation' => 'https://www.drupal.org/node/2487215')), E_USER_WARNING);
@@ -976,7 +982,13 @@
   }
   $missing = &drupal_static('drupal_get_filename:missing');
   if (isset($missing['#write_cache'])) {
-    unset($missing['#write_cache']);
+    if (!isset($missing['#cache_merge_done'])) {
+      $cache = cache_get('drupal_get_filename:missing', 'cache_bootstrap');
+      if (isset($cache->data)) {
+        $missing = $cache->data + $missing;
+      }
+    }
+    $missing['#write_cache'] = NULL;
     cache_set('drupal_get_filename:missing', $missing, 'cache_bootstrap');
   }
 }
@@ -2537,11 +2549,6 @@
   // the install or upgrade process.
   spl_autoload_register('drupal_autoload_class');
   spl_autoload_register('drupal_autoload_interface');
-
-  // Reset the drupal_get_filename() static missing filenames cache as it
-  // may have previously been initialized without the database being
-  // available.
-  drupal_static_reset('drupal_get_filename:missing'); 
 }
 
 /**
diff -u b/modules/simpletest/tests/bootstrap.test b/modules/simpletest/tests/bootstrap.test
--- b/modules/simpletest/tests/bootstrap.test
+++ b/modules/simpletest/tests/bootstrap.test
@@ -382,7 +382,7 @@
   }
 
   /**
-   * Whether the filename test triggered the right error. 
+   * Whether the filename test triggered the right error.
    *
    * Used by BootstrapGetFilenameTestCase::testDrupalGetFilename().
    *