diff --git a/lib/galaxy/datatypes/sequence.py b/lib/galaxy/datatypes/sequence.py
index 9c84fc487e64..4b580530ade5 100644
--- a/lib/galaxy/datatypes/sequence.py
+++ b/lib/galaxy/datatypes/sequence.py
@@ -357,7 +357,9 @@ def set_meta(self, dataset: DatasetProtocol, overwrite: bool = True, **kwd) -> N
         sequences = 0
         with compression_utils.get_fileobj(dataset.get_file_name()) as fh:
             for line in fh:
-                if line.startswith(">"):
+                if not line:
+                    continue
+                elif line[0] == ">":
                     sequences += 1
                     data_lines += 1
                 else: