diff --git a/lib/route.js b/lib/route.js
index a782c97e85..0e686fc596 100644
--- a/lib/route.js
+++ b/lib/route.js
@@ -327,7 +327,8 @@ function buildRouting (options) {
               schemaController.setupValidator(this[kOptions])
             }
             try {
-              compileSchemasForValidation(context, opts.validatorCompiler || schemaController.validatorCompiler)
+              const isCustom = typeof opts?.validatorCompiler === 'function' || schemaController.isCustomValidatorCompiler
+              compileSchemasForValidation(context, opts.validatorCompiler || schemaController.validatorCompiler, isCustom)
             } catch (error) {
               throw new FST_ERR_SCH_VALIDATION_BUILD(opts.method, url, error.message)
             }
diff --git a/lib/schema-controller.js b/lib/schema-controller.js
index 1484019cb9..78c4437678 100644
--- a/lib/schema-controller.js
+++ b/lib/schema-controller.js
@@ -25,7 +25,9 @@ function buildSchemaController (parentSchemaCtrl, opts) {
 
   const option = {
     bucket: (opts && opts.bucket) || buildSchemas,
-    compilersFactory
+    compilersFactory,
+    isCustomValidatorCompiler: typeof opts?.compilersFactory?.buildValidator === 'function',
+    isCustomSerializerCompiler: typeof opts?.compilersFactory?.buildValidator === 'function'
   }
 
   return new SchemaController(undefined, option)
@@ -37,6 +39,8 @@ class SchemaController {
     this.addedSchemas = false
 
     this.compilersFactory = this.opts.compilersFactory
+    this.isCustomValidatorCompiler = this.opts.isCustomValidatorCompiler || false
+    this.isCustomSerializerCompiler = this.opts.isCustomSerializerCompiler || false
 
     if (parent) {
       this.schemaBucket = this.opts.bucket(parent.getSchemas())
@@ -65,10 +69,12 @@ class SchemaController {
   // Schema Controller compilers holder
   setValidatorCompiler (validatorCompiler) {
     this.validatorCompiler = validatorCompiler
+    this.isCustomValidatorCompiler = true
   }
 
   setSerializerCompiler (serializerCompiler) {
     this.serializerCompiler = serializerCompiler
+    this.isCustomSerializerCompiler = true
   }
 
   getValidatorCompiler () {
diff --git a/lib/validation.js b/lib/validation.js
index 46ed81c804..939b5c5386 100644
--- a/lib/validation.js
+++ b/lib/validation.js
@@ -32,7 +32,7 @@ function compileSchemasForSerialization (context, compile) {
     }, {})
 }
 
-function compileSchemasForValidation (context, compile) {
+function compileSchemasForValidation (context, compile, isCustom) {
   const { schema } = context
   if (!schema) {
     return
@@ -41,8 +41,9 @@ function compileSchemasForValidation (context, compile) {
   const { method, url } = context.config || {}
 
   const headers = schema.headers
-  if (headers && Object.getPrototypeOf(headers) !== Object.prototype) {
-    // do not mess with non-literals, e.g. Joi schemas
+  // the or part is used for backward compatibility
+  if (headers && (isCustom || Object.getPrototypeOf(headers) !== Object.prototype)) {
+    // do not mess with schema when custom validator applied, e.g. Joi, Typebox
     context[headersSchema] = compile({ schema: headers, method, url, httpPart: 'headers' })
   } else if (headers) {
     // The header keys are case insensitive
diff --git a/test/internals/validation.test.js b/test/internals/validation.test.js
index 320f39bf5d..75e99597ea 100644
--- a/test/internals/validation.test.js
+++ b/test/internals/validation.test.js
@@ -268,6 +268,21 @@ test('build schema - headers are not lowercased in case of custom object', t =>
   })
 })
 
+test('build schema - headers are not lowercased in case of custom validator provided', t => {
+  t.plan(1)
+
+  class Headers {}
+  const opts = {
+    schema: {
+      headers: new Headers()
+    }
+  }
+  validation.compileSchemasForValidation(opts, ({ schema, method, url, httpPart }) => {
+    t.type(schema, Headers)
+    return () => {}
+  }, true)
+})
+
 test('build schema - uppercased headers are not included', t => {
   t.plan(1)
   const opts = {
diff --git a/test/schema-feature.test.js b/test/schema-feature.test.js
index af82cd4651..35c9f46861 100644
--- a/test/schema-feature.test.js
+++ b/test/schema-feature.test.js
@@ -1779,3 +1779,28 @@ test('Should return a human-friendly error if response status codes are not spec
     t.match(err.message, 'Failed building the serialization schema for GET: /, due to error response schemas should be nested under a valid status code, e.g { 2xx: { type: "object" } }')
   })
 })
+
+test('setSchemaController: custom validator instance should not mutate headers schema', async t => {
+  t.plan(2)
+  class Headers {}
+  const fastify = Fastify()
+
+  fastify.setSchemaController({
+    compilersFactory: {
+      buildValidator: function () {
+        return ({ schema, method, url, httpPart }) => {
+          t.type(schema, Headers)
+          return () => {}
+        }
+      }
+    }
+  })
+
+  fastify.get('/', {
+    schema: {
+      headers: new Headers()
+    }
+  }, () => {})
+
+  await fastify.ready()
+})
diff --git a/test/schema-validation.test.js b/test/schema-validation.test.js
index 05ce41be5a..e245a17342 100644
--- a/test/schema-validation.test.js
+++ b/test/schema-validation.test.js
@@ -1017,3 +1017,22 @@ test("The same $id in route's schema must not overwrite others", t => {
     t.same(res.payload, 'ok')
   })
 })
+
+test('Custom validator compiler should not mutate schema', async t => {
+  t.plan(2)
+  class Headers {}
+  const fastify = Fastify()
+
+  fastify.setValidatorCompiler(({ schema, method, url, httpPart }) => {
+    t.type(schema, Headers)
+    return () => {}
+  })
+
+  fastify.get('/', {
+    schema: {
+      headers: new Headers()
+    }
+  }, () => {})
+
+  await fastify.ready()
+})