diff --git a/lib/galaxy/model/orm/engine_factory.py b/lib/galaxy/model/orm/engine_factory.py
index 886a4e3462ab..374c53219c73 100644
--- a/lib/galaxy/model/orm/engine_factory.py
+++ b/lib/galaxy/model/orm/engine_factory.py
@@ -12,6 +12,7 @@
     exc,
 )
 from sqlalchemy.engine import Engine
+from sqlalchemy.pool import NullPool
 
 log = logging.getLogger(__name__)
 
@@ -101,8 +102,13 @@ def after_cursor_execute(conn, cursor, statement, parameters, context, executema
                     pass
 
     engine_options = engine_options or {}
-    engine_options = set_sqlite_connect_args(engine_options, url)
-    engine = create_engine(url, **engine_options, future=True)
+    if url.startswith("sqlite://"):
+        set_sqlite_connect_args(engine_options, url)
+
+    if url.startswith("sqlite://") and url not in ("sqlite:///:memory:", "sqlite://"):
+        engine = create_engine(url, **engine_options, poolclass=NullPool, future=True)
+    else:
+        engine = create_engine(url, **engine_options, future=True)
 
     # Prevent sharing connection across fork: https://docs.sqlalchemy.org/en/14/core/pooling.html#using-connection-pools-with-multiprocessing-or-os-fork
     register_after_fork(engine, lambda e: e.dispose())
@@ -123,13 +129,11 @@ def checkout(dbapi_connection, connection_record, connection_proxy):
     return engine
 
 
-def set_sqlite_connect_args(engine_options: Dict, url: str):
+def set_sqlite_connect_args(engine_options: Dict, url: str) -> None:
     """
     Add or update `connect_args` in `engine_options` if db is sqlite.
     Set check_same_thread to False for sqlite, handled by request-specific session.
     See https://fastapi.tiangolo.com/tutorial/sql-databases/#note
     """
-    if url.startswith("sqlite://"):
-        connect_args = engine_options.setdefault("connect_args", {})
-        connect_args["check_same_thread"] = False
-    return engine_options
+    connect_args = engine_options.setdefault("connect_args", {})
+    connect_args["check_same_thread"] = False
diff --git a/test/unit/data/model/test_engine_factory.py b/test/unit/data/model/test_engine_factory.py
index 947664865f3e..361fc1f608d3 100644
--- a/test/unit/data/model/test_engine_factory.py
+++ b/test/unit/data/model/test_engine_factory.py
@@ -7,28 +7,28 @@
 class TestSetSqliteConnectArgs:
     def test_engine_options_empty(self):
         engine_options = {}  # type: ignore[var-annotated]
-        updated = set_sqlite_connect_args(engine_options, SQLITE_URL)
-        assert updated == {"connect_args": {"check_same_thread": False}}
+        set_sqlite_connect_args(engine_options, SQLITE_URL)
+        assert engine_options == {"connect_args": {"check_same_thread": False}}
 
     def test_update_nonempty_engine_options(self):
         engine_options = {"foo": "some foo"}
-        updated = set_sqlite_connect_args(engine_options, SQLITE_URL)
-        assert len(updated) == 2
-        assert updated["foo"] == "some foo"
-        assert updated["connect_args"] == {"check_same_thread": False}
+        set_sqlite_connect_args(engine_options, SQLITE_URL)
+        assert len(engine_options) == 2
+        assert engine_options["foo"] == "some foo"
+        assert engine_options["connect_args"] == {"check_same_thread": False}  # type:ignore[comparison-overlap]
 
     def test_overwrite_connect_args(self):
         engine_options = {"foo": "some foo", "connect_args": {"check_same_thread": True}}
-        updated = set_sqlite_connect_args(engine_options, SQLITE_URL)
-        assert len(updated) == 2
-        assert updated["foo"] == "some foo"
-        assert updated["connect_args"] == {"check_same_thread": False}
+        set_sqlite_connect_args(engine_options, SQLITE_URL)
+        assert len(engine_options) == 2
+        assert engine_options["foo"] == "some foo"
+        assert engine_options["connect_args"] == {"check_same_thread": False}
 
     def test_update_nonempty_connect_args(self):
         engine_options = {"foo": "some foo", "connect_args": {"bar": "some bar"}}
-        updated = set_sqlite_connect_args(engine_options, SQLITE_URL)
-        assert len(updated) == 2
-        assert updated["foo"] == "some foo"
-        assert len(updated["connect_args"]) == 2
-        assert updated["connect_args"]["check_same_thread"] is False
-        assert updated["connect_args"]["bar"] == "some bar"
+        set_sqlite_connect_args(engine_options, SQLITE_URL)
+        assert len(engine_options) == 2
+        assert engine_options["foo"] == "some foo"
+        assert len(engine_options["connect_args"]) == 2
+        assert engine_options["connect_args"]["check_same_thread"] is False  # type:ignore[index]
+        assert engine_options["connect_args"]["bar"] == "some bar"  # type:ignore[index]