diff --git a/pycytominer/cyto_utils/cell_locations.py b/pycytominer/cyto_utils/cell_locations.py
index 5c4edeb7..9906317c 100644
--- a/pycytominer/cyto_utils/cell_locations.py
+++ b/pycytominer/cyto_utils/cell_locations.py
@@ -177,7 +177,14 @@ def _download_s3(self, uri: str):
 
         self.s3.download_file(bucket, key, tmp_file.name)
 
-        return tmp_file.name
+        # Check if the downloaded file exists and has a size greater than 0
+        tmp_file_path = pathlib.Path(tmp_file.name)
+        if tmp_file_path.exists() and tmp_file_path.stat().st_size > 0:
+            return tmp_file.name
+        else:
+            raise ValueError(
+                f"Downloaded file '{tmp_file.name}' is empty or does not exist."
+            )
 
     def _load_metadata(self):
         """Load the metadata into a Pandas DataFrame