diff --git a/pandas/io/pytables.py b/pandas/io/pytables.py
index 91f7b2afec56c..3659e7247495d 100644
--- a/pandas/io/pytables.py
+++ b/pandas/io/pytables.py
@@ -30,6 +30,7 @@
 from pandas._config import (
     config,
     get_option,
+    using_copy_on_write,
     using_pyarrow_string_dtype,
 )
 
@@ -3297,6 +3298,10 @@ def read(
 
         if len(dfs) > 0:
             out = concat(dfs, axis=1, copy=True)
+            if using_copy_on_write():
+                # with CoW, concat ignores the copy keyword. Here, we still want
+                # to copy to enforce optimized column-major layout
+                out = out.copy()
             out = out.reindex(columns=items, copy=False)
             return out