diff --git a/ehrql/__main__.py b/ehrql/__main__.py
index 286abdd7e..5663b0c4d 100644
--- a/ehrql/__main__.py
+++ b/ehrql/__main__.py
@@ -2,6 +2,7 @@
 import logging
 import os
 import sys
+import traceback
 import warnings
 from argparse import ArgumentParser, ArgumentTypeError, RawTextHelpFormatter
 from pathlib import Path
@@ -109,6 +110,17 @@ def main(args, environ=None):
         # Handle errors encountered while reading user-supplied data
         print(f"{exc.__class__.__name__}: {exc}", file=sys.stderr)
         sys.exit(1)
+    except Exception as exc:
+        # For functions which take a `backend_class` give that class the chance to set
+        # the appropriate exit status for any errors
+        if backend_class := kwargs.get("backend_class"):
+            if exit_status := backend_class(environ).get_exit_status_for_exception(
+                exc
+            ):  # pragma: no branch
+                # log the traceback to stderr to aid debugging
+                traceback.print_exc()
+                sys.exit(exit_status)
+        raise
     finally:
         root_logger.setLevel(orig_log_level)
 
diff --git a/ehrql/backends/base.py b/ehrql/backends/base.py
index c6126a0a4..d5866f02c 100644
--- a/ehrql/backends/base.py
+++ b/ehrql/backends/base.py
@@ -41,6 +41,9 @@ def modify_query_pre_reify(self, query):
         """
         return query
 
+    def get_exit_status_for_exception(self, exception):
+        return None
+
 
 class SQLBackend(BaseBackend):
     query_engine_class = None
diff --git a/ehrql/backends/tpp.py b/ehrql/backends/tpp.py
index dae008e16..050d4af65 100644
--- a/ehrql/backends/tpp.py
+++ b/ehrql/backends/tpp.py
@@ -126,6 +126,34 @@ def modify_query_variables(self, variables):
         )
         return variables
 
+    def get_exit_status_for_exception(self, exception):
+        # Checking for "DatabaseError" in the MRO means we can identify database errors without
+        # referencing a specific driver.  Both pymssql and presto/trino-python-client raise
+        # exceptions derived from a DatabaseError parent class
+
+        # Ignore errors which don't look like database errors
+        if "DatabaseError" not in str(exception.__class__.mro()):
+            return
+
+        # Exit with specific exit codes to help identify known issues
+        transient_errors = [
+            "Unexpected EOF from the server",
+            "DBPROCESS is dead or not enabled",
+        ]
+        if any(message in str(exception) for message in transient_errors):
+            exception.add_note(f"\nIntermittent database error: {exception}")
+            return 3
+
+        if "Invalid object name 'CodedEvent_SNOMED'" in str(exception):
+            exception.add_note(
+                "\nCodedEvent_SNOMED table is currently not available.\n"
+                "This is likely due to regular database maintenance."
+            )
+            return 4
+
+        exception.add_note(f"\nDatabase error: {exception}")
+        return 5
+
     allowed_patients = MappedTable(
         # This table has its name for historical reasons, and reads slightly oddly: it
         # should be interpreted as "allowed patients with regard to type one dissents"
diff --git a/tests/acceptance/test_embedded_study.py b/tests/acceptance/test_embedded_study.py
index 8c6549897..968b51de3 100644
--- a/tests/acceptance/test_embedded_study.py
+++ b/tests/acceptance/test_embedded_study.py
@@ -4,6 +4,7 @@
 
 from ehrql.file_formats import FILE_FORMATS
 from tests.lib.fixtures import (
+    database_operational_error_dataset_definition,
     invalid_dataset_attribute_dataset_definition,
     invalid_dataset_query_model_error_definition,
     no_dataset_attribute_dataset_definition,
@@ -74,6 +75,20 @@ def test_parameterised_dataset_definition_with_bad_param(study, mssql_database,
     )
 
 
+def test_generate_dataset_with_database_error(study, mssql_database):
+    mssql_database.setup(
+        Patient(Patient_ID=1, DateOfBirth=datetime(1934, 5, 5)),
+        AllowedPatientsWithTypeOneDissent(Patient_ID=1),
+    )
+
+    # This dataset definition triggers an OperationalError by implementing date
+    # arithmetic that results in an out of bounds date (after 9999-12-31)
+    study.setup_from_string(database_operational_error_dataset_definition)
+    with pytest.raises(SystemExit) as err:
+        study.generate(mssql_database, "ehrql.backends.tpp.TPPBackend")
+    assert err.value.code == 5
+
+
 def test_dump_dataset_sql_happy_path(study, mssql_database):
     study.setup_from_string(trivial_dataset_definition)
     study.dump_dataset_sql()
diff --git a/tests/integration/backends/test_emis.py b/tests/integration/backends/test_emis.py
index 2a4d06182..1896f7b58 100644
--- a/tests/integration/backends/test_emis.py
+++ b/tests/integration/backends/test_emis.py
@@ -1,6 +1,8 @@
 from datetime import date, datetime
 
+import pytest
 import sqlalchemy
+from trino import exceptions as trino_exceptions
 
 from ehrql import create_dataset
 from ehrql.backends.emis import EMISBackend
@@ -78,6 +80,28 @@ def get_all_backend_columns_with_types(trino_database):
             temp_table.drop(trino_database.engine())
 
 
+@pytest.mark.parametrize(
+    "exception",
+    [
+        # These are trino errors that we may want to support in future with
+        # custom exit codes, but currently inherit from the base method
+        # Database errors
+        trino_exceptions.DatabaseError,
+        # OperationError is a subclass of DatabaseError
+        trino_exceptions.OperationalError,
+        # TrinoQueryError is encountered for over-complex/over-nested queries
+        trino_exceptions.TrinoQueryError,
+        # TrinoUserError is encountered for out of range numbers
+        trino_exceptions.TrinoUserError,
+        # TrinoUserError is encountered for bad/out of range dates
+        trino_exceptions.TrinoDataError,
+    ],
+)
+def test_backend_exceptions(exception):
+    backend = EMISBackend()
+    assert backend.get_exit_status_for_exception(exception) is None
+
+
 @register_test_for(emis.clinical_events)
 def test_clinical_events(select_all_emis):
     results = select_all_emis(
diff --git a/tests/integration/backends/test_tpp.py b/tests/integration/backends/test_tpp.py
index c36f52f97..7803fcd1b 100644
--- a/tests/integration/backends/test_tpp.py
+++ b/tests/integration/backends/test_tpp.py
@@ -3,6 +3,7 @@
 
 import pytest
 import sqlalchemy
+from pymssql import exceptions as pymssql_exceptions
 
 from ehrql import create_dataset
 from ehrql.backends.tpp import TPPBackend
@@ -132,6 +133,48 @@ def get_all_backend_columns_with_types(mssql_database):
         yield table, column, column_type, column_args
 
 
+@pytest.mark.parametrize(
+    "exception,exit_code,custom_err",
+    [
+        (
+            pymssql_exceptions.OperationalError("Unexpected EOF from the server"),
+            3,
+            "Intermittent database error",
+        ),
+        (
+            pymssql_exceptions.OperationalError("DBPROCESS is dead or not enabled"),
+            3,
+            "Intermittent database error",
+        ),
+        (
+            pymssql_exceptions.OperationalError(
+                "Invalid object name 'CodedEvent_SNOMED'"
+            ),
+            4,
+            "CodedEvent_SNOMED table is currently not available",
+        ),
+        (pymssql_exceptions.DataError("Database data error"), 5, "Database error"),
+        (
+            pymssql_exceptions.InternalError("Other database internal error"),
+            5,
+            "Database error",
+        ),
+        (
+            pymssql_exceptions.DatabaseError("A plain old database error"),
+            5,
+            "Database error",
+        ),
+        (Exception("Other non-database error exception"), None, None),
+    ],
+)
+def test_backend_exceptions(exception, exit_code, custom_err):
+    backend = TPPBackend()
+    assert backend.get_exit_status_for_exception(exception) == exit_code
+
+    if custom_err is not None:  # pragma: no cover
+        assert any(custom_err in note for note in exception.__notes__)
+
+
 @register_test_for(tpp.addresses)
 def test_addresses(select_all_tpp):
     results = select_all_tpp(
diff --git a/tests/lib/fixtures.py b/tests/lib/fixtures.py
index 2674fb9e8..b16bfc2e7 100644
--- a/tests/lib/fixtures.py
+++ b/tests/lib/fixtures.py
@@ -1,3 +1,14 @@
+database_operational_error_dataset_definition = """
+from ehrql import Dataset, years
+from ehrql.tables.core import patients
+
+dataset = Dataset()
+dataset.define_population(patients.date_of_birth.year >= 1900)
+dataset.extended_dob = patients.date_of_birth + years(9999)
+
+dataset.configure_dummy_data(population_size=10)
+"""
+
 trivial_dataset_definition = """
 from ehrql import Dataset
 from ehrql.tables.tpp import patients