diff --git a/changelog.d/17736.bugfix b/changelog.d/17736.bugfix
new file mode 100644
index 0000000000..0d3fd06962
--- /dev/null
+++ b/changelog.d/17736.bugfix
@@ -0,0 +1 @@
+Fix saving of PNG thumbnails, when the original image is in the CMYK color space.
diff --git a/synapse/media/thumbnailer.py b/synapse/media/thumbnailer.py
index ee1118a53a..3845067835 100644
--- a/synapse/media/thumbnailer.py
+++ b/synapse/media/thumbnailer.py
@@ -206,7 +206,7 @@ def crop(self, width: int, height: int, output_type: str) -> BytesIO:
     def _encode_image(self, output_image: Image.Image, output_type: str) -> BytesIO:
         output_bytes_io = BytesIO()
         fmt = self.FORMATS[output_type]
-        if fmt == "JPEG":
+        if fmt == "JPEG" or fmt == "PNG" and output_image.mode == "CMYK":
             output_image = output_image.convert("RGB")
         output_image.save(output_bytes_io, fmt, quality=80)
         return output_bytes_io