diff --git a/src/npe2/io_utils.py b/src/npe2/io_utils.py
index 5bddae3f..109f596a 100644
--- a/src/npe2/io_utils.py
+++ b/src/npe2/io_utils.py
@@ -3,6 +3,7 @@
 from collections.abc import Sequence
 from typing import (
     TYPE_CHECKING,
+    Any,
     Literal,
     cast,
     overload,
@@ -157,20 +158,33 @@ def _read(
         "No readers to try. Expected an exception before this point."
     )
 
+    tried_reader = False
     for rdr in chosen_compatible_readers:
         read_func = rdr.exec(
             kwargs={"path": paths, "stack": stack, "_registry": _pm.commands}
         )
         if read_func is not None:
+            tried_reader = True
             # if the reader function raises an exception here, we don't try to catch it
-            if layer_data := read_func(paths, stack=stack):
+            layer_data = read_func(paths, stack=stack)
+            if plugin_name and _is_null_layer_sentinel(layer_data):
+                # we don't return null layers if the user selected a plugin,
+                # so that we can raise a meaningful error
+                continue
+            if layer_data:
                 return (layer_data, rdr) if return_reader else layer_data
 
     if plugin_name:
-        raise ValueError(
-            f"Reader {plugin_name!r} was selected to open "
-            + f"{paths!r}, but returned no data."
-        )
+        if tried_reader:
+            raise ValueError(
+                f"Reader {plugin_name!r} was selected to open "
+                + f"{paths!r}, but returned no data."
+            )
+        else:
+            raise ValueError(
+                f"Reader {plugin_name!r} was selected to open "
+                + f"{paths!r}, but refused the file."
+            )
     raise ValueError(f"No readers returned data for {paths!r}")
 
 
@@ -256,6 +270,29 @@ def _get_compatible_readers_by_choice(
     return chosen_compatible_readers
 
 
+def _is_null_layer_sentinel(layer_data: Any) -> bool:
+    """Checks if the layer data returned from a reader function indicates an
+    empty file. The sentinel value used for this is ``[(None,)]``.
+
+    Parameters
+    ----------
+    layer_data : LayerData
+        The layer data returned from a reader function to check
+
+    Returns
+    -------
+    bool
+        True, if the layer_data indicates an empty file, False otherwise
+    """
+    return (
+        isinstance(layer_data, list)
+        and len(layer_data) == 1
+        and isinstance(layer_data[0], tuple)
+        and len(layer_data[0]) == 1
+        and layer_data[0][0] is None
+    )
+
+
 @overload
 def _write(
     path: str,
diff --git a/tests/test__io_utils.py b/tests/test__io_utils.py
index 4c101ae7..08733c68 100644
--- a/tests/test__io_utils.py
+++ b/tests/test__io_utils.py
@@ -78,21 +78,67 @@ def read(paths):
         return read
 
     # "gooby-again" isn't used even though given plugin starts with the same name
-    # if an error is thrown here, it means we selected the wrong plugin
-    io_utils._read(["some.fzzy"], plugin_name=short_name, stack=False, _pm=pm)
+    # we check that the thrown error is from "gooby" NOT "gooby-again"
+    with pytest.raises(
+        ValueError, match=f"Reader {short_name!r} was selected .* but returned no data"
+    ):
+        io_utils._read(["some.fzzy"], plugin_name=short_name, stack=False, _pm=pm)
+
+
+def test_read_fails_with_refused_reader():
+    pm = PluginManager()
+    plugin_name = "always-fails"
+    plugin = DynamicPlugin(plugin_name, plugin_manager=pm)
+    plugin.register()
+
+    @plugin.contribute.reader(filename_patterns=["*.fzzy"])
+    def get_read(path):
+        return None
+
+    with pytest.raises(
+        ValueError, match=f"Reader {plugin_name!r} was selected .* refused the file"
+    ):
+        io_utils._read(["some.fzzy"], plugin_name=plugin_name, stack=False, _pm=pm)
+
+    with pytest.raises(ValueError, match="No readers returned data"):
+        io_utils._read(["some.fzzy"], stack=False, _pm=pm)
 
 
-def test_read_fails():
+def test_read_fails_with_null_layer():
     pm = PluginManager()
     plugin_name = "always-fails"
     plugin = DynamicPlugin(plugin_name, plugin_manager=pm)
     plugin.register()
 
+    def reader_func(path):
+        return [(None,)]
+
     @plugin.contribute.reader(filename_patterns=["*.fzzy"])
     def get_read(path):
+        return reader_func
+
+    with pytest.raises(
+        ValueError, match=f"Reader {plugin_name!r} was selected .* returned no data"
+    ):
+        io_utils._read(["some.fzzy"], plugin_name=plugin_name, stack=False, _pm=pm)
+
+
+def test_read_fails_with_reader_returning_none():
+    pm = PluginManager()
+    plugin_name = "none-reader"
+    plugin = DynamicPlugin(plugin_name, plugin_manager=pm)
+    plugin.register()
+
+    def reader_func(path):
         return None
 
-    with pytest.raises(ValueError, match=f"Reader {plugin_name!r} was selected"):
+    @plugin.contribute.reader(filename_patterns=["*.fzzy"])
+    def get_read(path):
+        return reader_func
+
+    with pytest.raises(
+        ValueError, match=f"Reader {plugin_name!r} was selected .* returned no data"
+    ):
         io_utils._read(["some.fzzy"], plugin_name=plugin_name, stack=False, _pm=pm)
 
     with pytest.raises(ValueError, match="No readers returned data"):
@@ -117,7 +163,10 @@ def test_read_with_no_compatible_reader():
 def test_read_with_reader_contribution_plugin(uses_sample_plugin):
     paths = ["some.fzzy"]
     chosen_reader = f"{SAMPLE_PLUGIN_NAME}.some_reader"
-    assert read(paths, stack=False, plugin_name=chosen_reader) == [(None,)]
+    with pytest.raises(
+        ValueError, match=f"Reader {chosen_reader!r} was selected .* returned no data"
+    ):
+        read(paths, stack=False, plugin_name=chosen_reader)
 
     # if the wrong contribution is passed we get useful error message
     chosen_reader = f"{SAMPLE_PLUGIN_NAME}.not_a_reader"