diff --git a/instrumentation/opentelemetry-instrumentation-dbapi/src/opentelemetry/instrumentation/dbapi/__init__.py b/instrumentation/opentelemetry-instrumentation-dbapi/src/opentelemetry/instrumentation/dbapi/__init__.py
index fb6416f52e..3afeb7e17c 100644
--- a/instrumentation/opentelemetry-instrumentation-dbapi/src/opentelemetry/instrumentation/dbapi/__init__.py
+++ b/instrumentation/opentelemetry-instrumentation-dbapi/src/opentelemetry/instrumentation/dbapi/__init__.py
@@ -460,6 +460,34 @@ def _populate_span(
         if self._db_api_integration.capture_parameters and len(args) > 1:
             span.set_attribute("db.statement.parameters", str(args[1]))
 
+    def _is_mysql_connector_cursor_prepared(self, cursor):  # pylint: disable=no-self-use
+        try:
+            from mysql.connector.cursor_cext import (  # pylint: disable=import-outside-toplevel
+                CMySQLCursorPrepared,
+                CMySQLCursorPreparedDict,
+                CMySQLCursorPreparedNamedTuple,
+                CMySQLCursorPreparedRaw,
+            )
+
+            if type(cursor) in [
+                CMySQLCursorPrepared,
+                CMySQLCursorPreparedDict,
+                CMySQLCursorPreparedNamedTuple,
+                CMySQLCursorPreparedRaw,
+            ]:
+                _logger.warning(
+                    "Adding sqlcomment to prepared MySQL statements is not supported. Please check OpenTelemetry configuration. Skipping."
+                )
+                return True
+
+        except ImportError as exc:
+            _logger.warning(
+                "Could not verify mysql.connector cursor, skipping sqlcomment: %s",
+                exc,
+            )
+
+        return False
+
     def get_operation_name(self, cursor, args):  # pylint: disable=no-self-use
         if args and isinstance(args[0], str):
             # Strip leading comments so we get the operation name.
@@ -494,49 +522,67 @@ def traced_execution(
         ) as span:
             if span.is_recording():
                 if args and self._commenter_enabled:
-                    try:
-                        args_list = list(args)
-
-                        # lazy capture of mysql-connector client version using cursor
-                        if (
-                            self._db_api_integration.database_system == "mysql"
-                            and self._db_api_integration.connect_module.__name__
-                            == "mysql.connector"
-                            and not self._db_api_integration.commenter_data[
-                                "mysql_client_version"
-                            ]
-                        ):
-                            self._db_api_integration.commenter_data[
-                                "mysql_client_version"
-                            ] = cursor._cnx._cmysql.get_client_info()
-
-                        commenter_data = dict(
-                            self._db_api_integration.commenter_data
+                    # If a mysql-connector cursor was created with prepared=True
+                    # then MySQL statements will be prepared and executed natively.
+                    # 1:1 sqlcomment and span correlation in instrumentation will
+                    # break, so sqlcomment is not supported for this use case.
+                    # This is here because a client app can use multiple cursors.
+                    is_prepared = False
+                    if (
+                        self._db_api_integration.database_system == "mysql"
+                        and self._db_api_integration.connect_module.__name__
+                        == "mysql.connector"
+                    ):
+                        is_prepared = self._is_mysql_connector_cursor_prepared(
+                            cursor
                         )
-                        if self._commenter_options.get(
-                            "opentelemetry_values", True
-                        ):
-                            commenter_data.update(
-                                **_get_opentelemetry_values()
-                            )
 
-                        # Filter down to just the requested attributes.
-                        commenter_data = {
-                            k: v
-                            for k, v in commenter_data.items()
-                            if self._commenter_options.get(k, True)
-                        }
-                        statement = _add_sql_comment(
-                            args_list[0], **commenter_data
-                        )
+                    if not is_prepared:
+                        try:
+                            args_list = list(args)
+
+                            # lazy capture of mysql-connector client version using cursor
+                            if (
+                                self._db_api_integration.database_system
+                                == "mysql"
+                                and self._db_api_integration.connect_module.__name__
+                                == "mysql.connector"
+                                and not self._db_api_integration.commenter_data[
+                                    "mysql_client_version"
+                                ]
+                            ):
+                                self._db_api_integration.commenter_data[
+                                    "mysql_client_version"
+                                ] = cursor._cnx._cmysql.get_client_info()
+
+                            commenter_data = dict(
+                                self._db_api_integration.commenter_data
+                            )
+                            if self._commenter_options.get(
+                                "opentelemetry_values", True
+                            ):
+                                commenter_data.update(
+                                    **_get_opentelemetry_values()
+                                )
+
+                            # Filter down to just the requested attributes.
+                            commenter_data = {
+                                k: v
+                                for k, v in commenter_data.items()
+                                if self._commenter_options.get(k, True)
+                            }
+                            statement = _add_sql_comment(
+                                args_list[0], **commenter_data
+                            )
 
-                        args_list[0] = statement
-                        args = tuple(args_list)
+                            args_list[0] = statement
+                            args = tuple(args_list)
 
-                    except Exception as exc:  # pylint: disable=broad-except
-                        _logger.exception(
-                            "Exception while generating sql comment: %s", exc
-                        )
+                        except Exception as exc:  # pylint: disable=broad-except
+                            _logger.exception(
+                                "Exception while generating sql comment: %s",
+                                exc,
+                            )
 
                 self._populate_span(span, cursor, *args)