diff --git a/lib/galaxy/jobs/handler.py b/lib/galaxy/jobs/handler.py
index 2472f874be37..0b4819f684f6 100644
--- a/lib/galaxy/jobs/handler.py
+++ b/lib/galaxy/jobs/handler.py
@@ -37,7 +37,10 @@
 )
 from galaxy.jobs.mapper import JobNotReadyException
 from galaxy.managers.jobs import get_jobs_to_check_at_startup
-from galaxy.model.base import transaction
+from galaxy.model.base import (
+    check_database_connection,
+    transaction,
+)
 from galaxy.structured_app import MinimalManagerApp
 from galaxy.util import unicodify
 from galaxy.util.custom_logging import get_logger
@@ -400,6 +403,7 @@ def __handle_waiting_jobs(self):
         the waiting queue. If the job has dependencies with errors, it is marked as having errors and removed from the
         queue. If the job belongs to an inactive user it is ignored.  Otherwise, the job is dispatched.
         """
+        check_database_connection(self.sa_session)
         # Pull all new jobs from the queue at once
         jobs_to_check = []
         resubmit_jobs = []
diff --git a/lib/galaxy/jobs/runners/pulsar.py b/lib/galaxy/jobs/runners/pulsar.py
index f9142ee8c59f..3925f4d8a7be 100644
--- a/lib/galaxy/jobs/runners/pulsar.py
+++ b/lib/galaxy/jobs/runners/pulsar.py
@@ -50,6 +50,7 @@
     AsynchronousJobState,
     JobState,
 )
+from galaxy.model.base import check_database_connection
 from galaxy.tool_util.deps import dependencies
 from galaxy.util import (
     galaxy_directory,
@@ -273,6 +274,7 @@ def url_to_destination(self, url):
         return JobDestination(runner="pulsar", params=url_to_destination_params(url))
 
     def check_watched_item(self, job_state):
+        check_database_connection(self.app.model.session())
         if self.use_mq:
             # Might still need to check pod IPs.
             job_wrapper = job_state.job_wrapper
@@ -972,6 +974,7 @@ def __async_update(self, full_status):
         galaxy_job_id = None
         remote_job_id = None
         try:
+            check_database_connection(self.sa_session)
             remote_job_id = full_status["job_id"]
             if len(remote_job_id) == 32:
                 # It is a UUID - assign_ids = uuid in destination params...
diff --git a/lib/galaxy/managers/base.py b/lib/galaxy/managers/base.py
index f3abe35e7ceb..15503678cb9a 100644
--- a/lib/galaxy/managers/base.py
+++ b/lib/galaxy/managers/base.py
@@ -54,7 +54,10 @@
     model,
 )
 from galaxy.model import tool_shed_install
-from galaxy.model.base import transaction
+from galaxy.model.base import (
+    check_database_connection,
+    transaction,
+)
 from galaxy.schema import ValueFilterQueryParams
 from galaxy.schema.fields import DecodedDatabaseIdField
 from galaxy.schema.storage_cleaner import (
@@ -315,6 +318,7 @@ def _one_with_recast_errors(self, query: Query) -> Query:
         :raises exceptions.ObjectNotFound: if no model is found
         :raises exceptions.InconsistentDatabase: if more than one model is found
         """
+        check_database_connection(self.session())
         # overridden to raise serializable errors
         try:
             return query.one()
diff --git a/lib/galaxy/model/base.py b/lib/galaxy/model/base.py
index 2aade3f4ff36..829bc773ec6d 100644
--- a/lib/galaxy/model/base.py
+++ b/lib/galaxy/model/base.py
@@ -58,6 +58,19 @@ def transaction(session: Union[scoped_session, Session, "SessionlessContext"]):
         yield
 
 
+def check_database_connection(session):
+    """
+    In the event of a database disconnect, if there exists an active database
+    transaction, that transaction becomes invalidated. Accessing the database
+    will raise sqlalchemy.exc.PendingRollbackError. This handles this situation
+    by rolling back the invalidated transaction.
+    Ref: https://docs.sqlalchemy.org/en/14/errors.html#can-t-reconnect-until-invalid-transaction-is-rolled-back
+    """
+    if session and session.connection().invalidated:
+        log.error("Database transaction rolled back due to invalid state.")
+        session.rollback()
+
+
 # TODO: Refactor this to be a proper class, not a bunch.
 class ModelMapping(Bunch):
     def __init__(self, model_modules, engine):