diff --git a/doc/source/whatsnew/v1.4.0.rst b/doc/source/whatsnew/v1.4.0.rst
index 2a718fdcf16e7..0430db0c9dda7 100644
--- a/doc/source/whatsnew/v1.4.0.rst
+++ b/doc/source/whatsnew/v1.4.0.rst
@@ -537,7 +537,8 @@ Indexing
 - Bug in :meth:`Index.get_indexer_non_unique` when index contains multiple ``np.datetime64("NaT")`` and ``np.timedelta64("NaT")`` (:issue:`43869`)
 - Bug in setting a scalar :class:`Interval` value into a :class:`Series` with ``IntervalDtype`` when the scalar's sides are floats and the values' sides are integers (:issue:`44201`)
 - Bug when setting string-backed :class:`Categorical` values that can be parsed to datetimes into a :class:`DatetimeArray` or :class:`Series` or :class:`DataFrame` column backed by :class:`DatetimeArray` failing to parse these strings (:issue:`44236`)
-
+- Bug in :meth:`Series.__setitem__` with an integer dtype other than ``int64`` setting with a ``range`` object unnecessarily upcasting to ``int64`` (:issue:`44261`)
+-
 
 Missing
 ^^^^^^^
diff --git a/pandas/core/dtypes/cast.py b/pandas/core/dtypes/cast.py
index c0ac9098ec7fc..8be4fc13ed991 100644
--- a/pandas/core/dtypes/cast.py
+++ b/pandas/core/dtypes/cast.py
@@ -2197,6 +2197,9 @@ def can_hold_element(arr: ArrayLike, element: Any) -> bool:
     tipo = maybe_infer_dtype_type(element)
 
     if dtype.kind in ["i", "u"]:
+        if isinstance(element, range):
+            return _dtype_can_hold_range(element, dtype)
+
         if tipo is not None:
             if tipo.kind not in ["i", "u"]:
                 if is_float(element) and element.is_integer():
@@ -2209,6 +2212,7 @@ def can_hold_element(arr: ArrayLike, element: Any) -> bool:
                 # i.e. nullable IntegerDtype; we can put this into an ndarray
                 #  losslessly iff it has no NAs
                 return not element._mask.any()
+
             return True
 
         # We have not inferred an integer from the dtype
@@ -2249,3 +2253,14 @@ def can_hold_element(arr: ArrayLike, element: Any) -> bool:
         return isinstance(element, bytes) and len(element) <= dtype.itemsize
 
     raise NotImplementedError(dtype)
+
+
+def _dtype_can_hold_range(rng: range, dtype: np.dtype) -> bool:
+    """
+    maybe_infer_dtype_type infers to int64 (and float64 for very large endpoints),
+    but in many cases a range can be held by a smaller integer dtype.
+    Check if this is one of those cases.
+    """
+    if not len(rng):
+        return True
+    return np.can_cast(rng[0], dtype) and np.can_cast(rng[-1], dtype)
diff --git a/pandas/tests/dtypes/cast/test_can_hold_element.py b/pandas/tests/dtypes/cast/test_can_hold_element.py
new file mode 100644
index 0000000000000..c4776f2a1e143
--- /dev/null
+++ b/pandas/tests/dtypes/cast/test_can_hold_element.py
@@ -0,0 +1,42 @@
+import numpy as np
+
+from pandas.core.dtypes.cast import can_hold_element
+
+
+def test_can_hold_element_range(any_int_numpy_dtype):
+    # GH#44261
+    dtype = np.dtype(any_int_numpy_dtype)
+    arr = np.array([], dtype=dtype)
+
+    rng = range(2, 127)
+    assert can_hold_element(arr, rng)
+
+    # negatives -> can't be held by uint dtypes
+    rng = range(-2, 127)
+    if dtype.kind == "i":
+        assert can_hold_element(arr, rng)
+    else:
+        assert not can_hold_element(arr, rng)
+
+    rng = range(2, 255)
+    if dtype == "int8":
+        assert not can_hold_element(arr, rng)
+    else:
+        assert can_hold_element(arr, rng)
+
+    rng = range(-255, 65537)
+    if dtype.kind == "u":
+        assert not can_hold_element(arr, rng)
+    elif dtype.itemsize < 4:
+        assert not can_hold_element(arr, rng)
+    else:
+        assert can_hold_element(arr, rng)
+
+    # empty
+    rng = range(-(10 ** 10), -(10 ** 10))
+    assert len(rng) == 0
+    # assert can_hold_element(arr, rng)
+
+    rng = range(10 ** 10, 10 ** 10)
+    assert len(rng) == 0
+    assert can_hold_element(arr, rng)
diff --git a/pandas/tests/series/indexing/test_setitem.py b/pandas/tests/series/indexing/test_setitem.py
index 5521bee09b19b..5f0710dfbb85a 100644
--- a/pandas/tests/series/indexing/test_setitem.py
+++ b/pandas/tests/series/indexing/test_setitem.py
@@ -6,6 +6,8 @@
 import numpy as np
 import pytest
 
+from pandas.core.dtypes.common import is_list_like
+
 from pandas import (
     Categorical,
     DataFrame,
@@ -622,6 +624,16 @@ def test_mask_key(self, obj, key, expected, val, indexer_sli):
         tm.assert_series_equal(obj, expected)
 
     def test_series_where(self, obj, key, expected, val, is_inplace):
+        if is_list_like(val) and len(val) < len(obj):
+            # Series.where is not valid here
+            if isinstance(val, range):
+                return
+
+            # FIXME: The remaining TestSetitemDT64IntoInt that go through here
+            #  are relying on technically-incorrect behavior because Block.where
+            #  uses np.putmask instead of expressions.where in those cases,
+            #  which has different length-checking semantics.
+
         mask = np.zeros(obj.shape, dtype=bool)
         mask[key] = True
 
@@ -973,6 +985,35 @@ def expected(self, obj, val):
         return Series(idx)
 
 
+class TestSetitemRangeIntoIntegerSeries(SetitemCastingEquivalents):
+    # GH#44261 Setting a range with sufficiently-small integers into
+    #  small-itemsize integer dtypes should not need to upcast
+
+    @pytest.fixture
+    def obj(self, any_int_numpy_dtype):
+        dtype = np.dtype(any_int_numpy_dtype)
+        ser = Series(range(5), dtype=dtype)
+        return ser
+
+    @pytest.fixture
+    def val(self):
+        return range(2, 4)
+
+    @pytest.fixture
+    def key(self):
+        return slice(0, 2)
+
+    @pytest.fixture
+    def expected(self, any_int_numpy_dtype):
+        dtype = np.dtype(any_int_numpy_dtype)
+        exp = Series([2, 3, 2, 3, 4], dtype=dtype)
+        return exp
+
+    @pytest.fixture
+    def inplace(self):
+        return True
+
+
 def test_setitem_int_as_positional_fallback_deprecation():
     # GH#42215 deprecated falling back to positional on __setitem__ with an
     #  int not contained in the index