diff --git a/UPGRADE.rst b/UPGRADE.rst
index a0202932b1cb..470246f12803 100644
--- a/UPGRADE.rst
+++ b/UPGRADE.rst
@@ -76,6 +76,15 @@ for example:
      dpkg -i matrix-synapse-py3_1.3.0+stretch1_amd64.deb
 
 
+Upgrading to **<NEXT_VERSION>**
+===============================
+
+Synapse will now log a warning on start up if used with a PostgreSQL database
+that has a non-recommended locale set.
+
+See [docs/postgres.md](docs/postgres.md) for details.
+
+
 Upgrading to v1.8.0
 ===================
 
diff --git a/changelog.d/6734.bugfix b/changelog.d/6734.bugfix
new file mode 100644
index 000000000000..79c6bab4d1c3
--- /dev/null
+++ b/changelog.d/6734.bugfix
@@ -0,0 +1 @@
+Warn if postgres database has a non-C locale, as that can cause issues when upgrading locales (e.g. due to upgrading OS).
diff --git a/docs/postgres.md b/docs/postgres.md
index 7cb1ad18d4ec..e0793ecee86b 100644
--- a/docs/postgres.md
+++ b/docs/postgres.md
@@ -32,7 +32,7 @@ Assuming your PostgreSQL database user is called `postgres`, first authenticate
     su - postgres
     # Or, if your system uses sudo to get administrative rights
     sudo -u postgres bash
-  
+
 Then, create a user ``synapse_user`` with:
 
     createuser --pwprompt synapse_user
@@ -63,6 +63,24 @@ You may need to enable password authentication so `synapse_user` can
 connect to the database. See
 <https://www.postgresql.org/docs/11/auth-pg-hba-conf.html>.
 
+### Fixing incorrect `COLLATE` or `CTYPE`
+
+Synapse will refuse to set up a new database if it has the wrong values of
+`COLLATE` and `CTYPE` set, and will log warnings on existing databases. Using
+different locales can cause issues if the locale library is updated from
+underneath the database, or if a different version of the locale is used on any
+replicas.
+
+The safest way to fix the issue is to take a dump and recreate the database with
+the correct `COLLATE` and `CTYPE` parameters (as per
+[docs/postgres.md](docs/postgres.md)). It is also possible to change the
+parameters on a live database and run a `REINDEX` on the entire database,
+however extreme care must be taken to avoid database corruption.
+
+Note that the above may fail with an error about duplicate rows if corruption
+has already occurred, and such duplicate rows will need to be manually removed.
+
+
 ## Tuning Postgres
 
 The default settings should be fine for most deployments. For larger
diff --git a/synapse/storage/engines/postgres.py b/synapse/storage/engines/postgres.py
index c84cb452b0c6..a077345960a9 100644
--- a/synapse/storage/engines/postgres.py
+++ b/synapse/storage/engines/postgres.py
@@ -13,8 +13,12 @@
 # See the License for the specific language governing permissions and
 # limitations under the License.
 
+import logging
+
 from ._base import IncorrectDatabaseSetup
 
+logger = logging.getLogger(__name__)
+
 
 class PostgresEngine(object):
     single_threaded = False
@@ -52,6 +56,44 @@ def check_database(self, db_conn, allow_outdated_version: bool = False):
                     "See docs/postgres.rst for more information." % (rows[0][0],)
                 )
 
+            txn.execute(
+                "SELECT datcollate, datctype FROM pg_database WHERE datname = current_database()"
+            )
+            collation, ctype = txn.fetchone()
+            if collation != "C":
+                logger.warning(
+                    "Database has incorrect collation of %r. Should be 'C'", collation
+                )
+
+            if ctype != "C":
+                logger.warning(
+                    "Database has incorrect ctype of %r. Should be 'C'", ctype
+                )
+
+    def check_new_database(self, txn):
+        """Gets called when setting up a brand new database. This allows us to
+        apply stricter checks on new databases versus existing database.
+        """
+
+        txn.execute(
+            "SELECT datcollate, datctype FROM pg_database WHERE datname = current_database()"
+        )
+        collation, ctype = txn.fetchone()
+
+        errors = []
+
+        if collation != "C":
+            errors.append("    - 'COLLATE' is set to %r. Should be 'C'" % (collation,))
+
+        if ctype != "C":
+            errors.append("    - 'CTYPE' is set to %r. Should be 'C'" % (collation,))
+
+        if errors:
+            raise IncorrectDatabaseSetup(
+                "Database is incorrectly configured:\n\n%s\n\n"
+                "See docs/postgres.md for more information." % ("\n".join(errors))
+            )
+
     def convert_param_style(self, sql):
         return sql.replace("?", "%s")
 
diff --git a/synapse/storage/engines/sqlite.py b/synapse/storage/engines/sqlite.py
index cbf52f51913e..641e49069758 100644
--- a/synapse/storage/engines/sqlite.py
+++ b/synapse/storage/engines/sqlite.py
@@ -59,6 +59,11 @@ def check_database(self, db_conn, allow_outdated_version: bool = False):
             if version < (3, 11, 0):
                 raise RuntimeError("Synapse requires sqlite 3.11 or above.")
 
+    def check_new_database(self, txn):
+        """Gets called when setting up a brand new database. This allows us to
+        apply stricter checks on new databases versus existing database.
+        """
+
     def convert_param_style(self, sql):
         return sql
 
diff --git a/synapse/storage/prepare_database.py b/synapse/storage/prepare_database.py
index e86984cd50b5..c285ef52a0ba 100644
--- a/synapse/storage/prepare_database.py
+++ b/synapse/storage/prepare_database.py
@@ -136,6 +136,11 @@ def _setup_new_database(cur, database_engine, data_stores):
         data_stores (list[str]): The names of the data stores to instantiate
             on the given database.
     """
+
+    # We're about to set up a brand new database so we check that its
+    # configured to our liking.
+    database_engine.check_new_database(cur)
+
     current_dir = os.path.join(dir_path, "schema", "full_schemas")
     directory_entries = os.listdir(current_dir)