diff --git a/CHANGES/3976.bugfix b/CHANGES/3976.bugfix
new file mode 100644
index 00000000000..4e567ff3a11
--- /dev/null
+++ b/CHANGES/3976.bugfix
@@ -0,0 +1 @@
+Accept istr keys in LooseHeaders type hints.
diff --git a/aiohttp/typedefs.py b/aiohttp/typedefs.py
index d7c97a435dd..3c42f6abe30 100644
--- a/aiohttp/typedefs.py
+++ b/aiohttp/typedefs.py
@@ -12,7 +12,13 @@
     Union,
 )
 
-from multidict import CIMultiDict, CIMultiDictProxy, MultiDict, MultiDictProxy
+from multidict import (
+    CIMultiDict,
+    CIMultiDictProxy,
+    MultiDict,
+    MultiDictProxy,
+    istr,
+)
 from yarl import URL
 
 DEFAULT_JSON_ENCODER = json.dumps
@@ -33,7 +39,8 @@
 Byteish = Union[bytes, bytearray, memoryview]
 JSONEncoder = Callable[[Any], str]
 JSONDecoder = Callable[[str], Any]
-LooseHeaders = Union[Mapping[str, str], _CIMultiDict, _CIMultiDictProxy]
+LooseHeaders = Union[Mapping[Union[str, istr], str], _CIMultiDict,
+                     _CIMultiDictProxy]
 RawHeaders = Tuple[Tuple[bytes, bytes], ...]
 StrOrURL = Union[str, URL]
 LooseCookies = Union[Iterable[Tuple[str, 'BaseCookie[str]']],