diff --git a/openmc/deplete/__init__.py b/openmc/deplete/__init__.py
index e49c4e69cf..721bd636cc 100644
--- a/openmc/deplete/__init__.py
+++ b/openmc/deplete/__init__.py
@@ -4,12 +4,26 @@ openmc.deplete
 
 A depletion front-end tool.
 """
+from sys import exit
+
+from h5py import get_config
 
 from .dummy_comm import DummyCommunicator
+
 try:
     from mpi4py import MPI
+
     comm = MPI.COMM_WORLD
     have_mpi = True
+    # check if running with MPI and if using parallel HDF5
+
+    if not get_config().mpi and comm.size > 1:
+        # Raise exception only on process 0
+        if comm.rank:
+            exit()
+        raise RuntimeError(
+            "Need parallel HDF5 installed to perform depletion with MPI"
+        )
 except ImportError:
     comm = DummyCommunicator()
     have_mpi = False