diff --git a/tests/test_preprocess.py b/tests/test_preprocess.py
index 7b169e8..0e9514b 100644
--- a/tests/test_preprocess.py
+++ b/tests/test_preprocess.py
@@ -26,6 +26,7 @@ def single_tree_example_ts():
         tables.mutations.add_row(site=j, derived_state="T", node=j)
     tables.sites.add_row(position=7, ancestral_state="FOOBAR")
     tables.mutations.add_row(site=6, derived_state="FOOBARD", node=6)
+    tables.compute_mutation_times()
     return tables.tree_sequence()
 
 
@@ -299,6 +300,23 @@ def test_sample_and_other_flags(self, bit):
             assert (node.flags & (1 << bit)) != 0
 
 
+def test_preprocess_calculate_mutation_times(tmpdir):
+    ts = msprime.sim_ancestry(5, sequence_length=1e4, random_seed=42)
+    ts = msprime.sim_mutations(ts, rate=0.1, random_seed=43)
+    assert ts.num_mutations > 0
+    # Wipe out mutation times
+    tables = ts.dump_tables()
+    tables.mutations.time = np.full_like(tables.mutations.time, tskit.UNKNOWN_TIME)
+    ts = tables.tree_sequence()
+    input_path = os.path.join(tmpdir, "test.trees")
+    ts.dump(input_path)
+    output_path = os.path.join(tmpdir, "test.trees")
+    with pytest.warns(UserWarning, match="All mutation times are unknown"):
+        preprocess.preprocess(input_path, output_path)
+    ts = tszip.load(output_path)
+    assert not np.any(tskit.is_unknown_time(ts.tables.mutations.time))
+
+
 @pytest.mark.parametrize("use_tszip", [True, False])
 def test_preprocess(tmpdir, use_tszip):
     input_path = os.path.join(tmpdir, "test_input.tszip")
diff --git a/tsbrowse/preprocess.py b/tsbrowse/preprocess.py
index fd7672b..26c9d28 100644
--- a/tsbrowse/preprocess.py
+++ b/tsbrowse/preprocess.py
@@ -1,6 +1,7 @@
 import dataclasses
 import json
 import pathlib
+import warnings
 
 import daiquiri
 import numba
@@ -514,6 +515,17 @@ def preprocess(tszip_path, output_path, show_progress=False):
         total=2 + len(preprocessors), desc="Processing", disable=not show_progress
     ) as pbar:
         ts = tszip.load(tszip_path)
+        # Check if all mutation times are unknown, calulate them if so
+        if np.all(tskit.is_unknown_time(ts.mutations_time)):
+            warnings.warn(
+                "All mutation times are unknown. Calculating mutation times"
+                " from tree sequence",
+                stacklevel=1,
+            )
+            tables = ts.dump_tables()
+            tables.compute_mutation_times()
+            ts = tables.tree_sequence()
+
         pbar.update(1)
 
         tszip.compress(ts, output_path)