diff --git a/lib/internal/blob.js b/lib/internal/blob.js
index 9c6be6981f5b88..ee8e1c75819ab9 100644
--- a/lib/internal/blob.js
+++ b/lib/internal/blob.js
@@ -56,6 +56,7 @@ const {
     ERR_INVALID_ARG_TYPE,
     ERR_INVALID_ARG_VALUE,
     ERR_INVALID_THIS,
+    ERR_INVALID_STATE,
     ERR_BUFFER_TOO_LARGE,
   },
 } = require('internal/errors');
@@ -74,6 +75,7 @@ const { queueMicrotask } = require('internal/process/task_queues');
 const kHandle = Symbol('kHandle');
 const kType = Symbol('kType');
 const kLength = Symbol('kLength');
+const kNotCloneable = Symbol('kNotCloneable');
 
 const disallowedTypeCharacters = /[^\u{0020}-\u{007E}]/u;
 
@@ -186,6 +188,11 @@ class Blob {
   }
 
   [kClone]() {
+    if (this[kNotCloneable]) {
+      // We do not currently allow file-backed Blobs to be cloned or passed across
+      // worker threads.
+      throw new ERR_INVALID_STATE.TypeError('File-backed Blobs are not cloneable');
+    }
     const handle = this[kHandle];
     const type = this[kType];
     const length = this[kLength];
@@ -438,7 +445,9 @@ function createBlobFromFilePath(path, options) {
     return lazyDOMException('The blob could not be read', 'NotReadableError');
   }
   const { 0: blob, 1: length } = maybeBlob;
-  return createBlob(blob, length, options?.type);
+  const res = createBlob(blob, length, options?.type);
+  res[kNotCloneable] = true;
+  return res;
 }
 
 module.exports = {
diff --git a/test/parallel/test-blob-file-backed.js b/test/parallel/test-blob-file-backed.js
index 225b660c7bbdb3..b25137a34c3d01 100644
--- a/test/parallel/test-blob-file-backed.js
+++ b/test/parallel/test-blob-file-backed.js
@@ -4,6 +4,7 @@ const common = require('../common');
 const {
   strictEqual,
   rejects,
+  throws,
 } = require('assert');
 const { TextDecoder } = require('util');
 const {
@@ -99,3 +100,14 @@ writeFileSync(testfile3, '');
   const reader = stream.getReader();
   await rejects(() => reader.read(), { name: 'NotReadableError' });
 })().then(common.mustCall());
+
+(async () => {
+  // We currently do not allow File-backed blobs to be cloned or transfered
+  // across worker threads. This is largely because the underlying FdEntry
+  // is bound to the Environment/Realm under which is was created.
+  const blob = await openAsBlob(__filename);
+  throws(() => structuredClone(blob), {
+    code: 'ERR_INVALID_STATE',
+    message: 'Invalid state: File-backed Blobs are not cloneable'
+  });
+})().then(common.mustCall());