diff --git a/.changelog/5328.changed b/.changelog/5328.changed
new file mode 100644
index 0000000000..94c13b2b6f
--- /dev/null
+++ b/.changelog/5328.changed
@@ -0,0 +1 @@
+`opentelemetry-api`: normalize empty environment propagation names to `_` in `EnvironmentSetter` and `EnvironmentGetter`
\ No newline at end of file
diff --git a/opentelemetry-api/src/opentelemetry/propagators/_envcarrier.py b/opentelemetry-api/src/opentelemetry/propagators/_envcarrier.py
index 0e51e2606f..5b597cece6 100644
--- a/opentelemetry-api/src/opentelemetry/propagators/_envcarrier.py
+++ b/opentelemetry-api/src/opentelemetry/propagators/_envcarrier.py
@@ -9,6 +9,8 @@
 
 
 def _normalize_key(key: str) -> str:
+    if not key:
+        return "_"
     result = re.sub(r"[^A-Za-z0-9_]", "_", key).upper()
     if result and result[0].isdigit():
         result = "_" + result
@@ -95,7 +97,7 @@ def set(
 
         Args:
             carrier: Dictionary to store environment variables
-            key: The key to set (will be converted to uppercase)
+            key: The key to set (normalized)
             value: The value to set
         """
         carrier[_normalize_key(key)] = value
diff --git a/opentelemetry-api/tests/propagators/test__envcarrier.py b/opentelemetry-api/tests/propagators/test__envcarrier.py
index 63aac7e958..8d00c62bd9 100644
--- a/opentelemetry-api/tests/propagators/test__envcarrier.py
+++ b/opentelemetry-api/tests/propagators/test__envcarrier.py
@@ -41,7 +41,7 @@ def test_already_valid(self):
         self.assertEqual(_normalize_key("ALREADY_VALID"), "ALREADY_VALID")
 
     def test_empty_string(self):
-        self.assertEqual(_normalize_key(""), "")
+        self.assertEqual(_normalize_key(""), "_")
 
 
 class TestIsNormalizedKey(unittest.TestCase):
@@ -94,6 +94,13 @@ def test_get_empty_value(self):
             result = getter.get({}, "empty_key")
             self.assertEqual(result, [""])
 
+    def test_get_empty_key_maps_to_underscore(self):
+        """Test empty key lookup uses the normalized underscore name."""
+        with patch.dict(os.environ, {"_": "underscore_value"}, clear=True):
+            getter = EnvironmentGetter()
+            result = getter.get({}, "")
+            self.assertEqual(result, ["underscore_value"])
+
     def test_get_with_special_characters(self):
         """Test environment variables with special characters."""
         with patch.dict(
@@ -234,6 +241,13 @@ def test_set_empty_value(self):
         setter.set(carrier, "empty_key", "")
         self.assertEqual(carrier, {"EMPTY_KEY": ""})
 
+    def test_set_empty_key_maps_to_underscore(self):
+        """Test setting an empty key uses the normalized underscore name."""
+        setter = EnvironmentSetter()
+        carrier = {}
+        setter.set(carrier, "", "value")
+        self.assertEqual(carrier, {"_": "value"})
+
     def test_does_not_modify_os_environ(self):
         """Test that setter does not modify os.environ."""
         setter = EnvironmentSetter()