diff --git a/docs/changelog.rst b/docs/changelog.rst
index e1c8a982..a7109ca3 100644
--- a/docs/changelog.rst
+++ b/docs/changelog.rst
@@ -9,6 +9,13 @@ Compatibility
 
 * Official Django 6.1 support.
 
+Improvements
+^^^^^^^^^^^^
+
+* Warn when ``--reuse-db`` is used with an in-memory SQLite database, since
+  such a database only lives for the duration of the process and can't be
+  reused between test runs.
+
 v4.14.0 (2026-08-10)
 --------------------
 
diff --git a/docs/database.rst b/docs/database.rst
index fcdd219a..9241077a 100644
--- a/docs/database.rst
+++ b/docs/database.rst
@@ -94,6 +94,11 @@ instantly be re used. This will allow much faster startup time for tests.
 This can be especially useful when running a few tests, when there are a lot
 of database tables to set up.
 
+Note that ``--reuse-db`` has no effect for an in-memory SQLite database (the
+default for SQLite): such a database only exists while the process is running,
+so there is nothing to reuse between runs. pytest-django emits a warning in
+this case.
+
 ``--reuse-db`` will not pick up schema changes between test runs. You must run
 the tests with ``--reuse-db --create-db`` to re-create the database according
 to the new schema. Running without ``--reuse-db`` is also possible, since the
diff --git a/pytest_django/fixtures.py b/pytest_django/fixtures.py
index 07af3153..2ac364a8 100644
--- a/pytest_django/fixtures.py
+++ b/pytest_django/fixtures.py
@@ -191,6 +191,24 @@ def django_db_setup(  # noqa: PLR0917
             **setup_databases_args,
         )
 
+    if django_db_keepdb and not django_db_createdb:
+        from django.db import connections
+
+        in_memory_aliases = sorted(
+            alias
+            for alias in aliases
+            if connections[alias].vendor == "sqlite" and connections[alias].is_in_memory_db()
+        )
+        if in_memory_aliases:
+            request.node.warn(
+                pytest.PytestWarning(
+                    "--reuse-db has no effect for the in-memory sqlite database(s) "
+                    f"{', '.join(repr(alias) for alias in in_memory_aliases)}: an in-memory "
+                    "database only exists for the duration of the process, so there "
+                    "is nothing to reuse between test runs."
+                )
+            )
+
     yield
 
     if not django_db_keepdb:
diff --git a/tests/test_db_setup.py b/tests/test_db_setup.py
index 3cb04dbf..b929c862 100644
--- a/tests/test_db_setup.py
+++ b/tests/test_db_setup.py
@@ -620,3 +620,46 @@ class Migration(migrations.Migration):
         assert result.ret == 0
         result.stdout.fnmatch_lines(["*test_something_without_db PASSED*"])
         result.stdout.no_fnmatch_line("*mark_migrations_run*")
+
+
+class TestSqliteReuseDbInMemory:
+    db_settings: ClassVar = {
+        "default": {
+            "ENGINE": "django.db.backends.sqlite3",
+            "NAME": ":memory:",
+        }
+    }
+
+    def test_reuse_db_warns_for_in_memory_database(self, django_pytester: DjangoPytester) -> None:
+        "--reuse-db can't reuse an in-memory database, so warn about it."
+        django_pytester.create_test_module(
+            """
+            import pytest
+
+            @pytest.mark.django_db
+            def test_inner():
+                pass
+        """
+        )
+
+        result = django_pytester.runpytest_subprocess("-v", "--reuse-db")
+        assert result.ret == 0
+        result.stdout.fnmatch_lines(
+            ["*--reuse-db has no effect for the in-memory sqlite database*"]
+        )
+
+    def test_no_warning_without_reuse_db(self, django_pytester: DjangoPytester) -> None:
+        "Without --reuse-db the warning must not be emitted."
+        django_pytester.create_test_module(
+            """
+            import pytest
+
+            @pytest.mark.django_db
+            def test_inner():
+                pass
+        """
+        )
+
+        result = django_pytester.runpytest_subprocess("-v")
+        assert result.ret == 0
+        result.stdout.no_fnmatch_line("*--reuse-db has no effect*")