diff --git a/src/ImageSharp/Formats/Png/PngEncoderCore.cs b/src/ImageSharp/Formats/Png/PngEncoderCore.cs
index ddef1c9cd9..ea94270f2f 100644
--- a/src/ImageSharp/Formats/Png/PngEncoderCore.cs
+++ b/src/ImageSharp/Formats/Png/PngEncoderCore.cs
@@ -3,6 +3,7 @@
 
 using System.Buffers;
 using System.Buffers.Binary;
+using System.Numerics;
 using System.Runtime.CompilerServices;
 using System.Runtime.InteropServices;
 using SixLabors.ImageSharp.Common.Helpers;
@@ -1527,7 +1528,24 @@ private void SanitizeAndSetEncoderOptions<TPixel>(
             {
                 // We can use the color data from the decoded metadata here.
                 // We avoid dithering by default to preserve the original colors.
-                this.derivedTransparencyIndex = metadata.ColorTable.Value.Span.IndexOf(Color.Transparent);
+                ReadOnlySpan<Color> palette = metadata.ColorTable.Value.Span;
+
+                // Certain operations perform alpha premultiplication, which can cause the color to change so we
+                // must search for the transparency index in the palette.
+                // Transparent pixels are much more likely to be found at the end of a palette.
+                int index = -1;
+                for (int i = palette.Length - 1; i >= 0; i--)
+                {
+                    Vector4 instance = palette[i].ToScaledVector4();
+                    if (instance.W == 0f)
+                    {
+                        index = i;
+                        break;
+                    }
+                }
+
+                this.derivedTransparencyIndex = index;
+
                 this.quantizer = new PaletteQuantizer(metadata.ColorTable.Value, new() { Dither = null }, this.derivedTransparencyIndex);
             }
             else
diff --git a/tests/ImageSharp.Tests/Formats/Png/PngEncoderTests.cs b/tests/ImageSharp.Tests/Formats/Png/PngEncoderTests.cs
index e70854b082..950f1d2e3a 100644
--- a/tests/ImageSharp.Tests/Formats/Png/PngEncoderTests.cs
+++ b/tests/ImageSharp.Tests/Formats/Png/PngEncoderTests.cs
@@ -8,6 +8,7 @@
 using SixLabors.ImageSharp.Formats.Webp;
 using SixLabors.ImageSharp.Metadata;
 using SixLabors.ImageSharp.PixelFormats;
+using SixLabors.ImageSharp.Processing;
 using SixLabors.ImageSharp.Processing.Processors.Quantization;
 using SixLabors.ImageSharp.Tests.TestUtilities;
 using SixLabors.ImageSharp.Tests.TestUtilities.ImageComparison;
@@ -678,6 +679,22 @@ public void Issue2469_Quantized_Encode_Artifacts<TPixel>(TestImageProvider<TPixe
         encoded.CompareToReferenceOutput(ImageComparer.Exact, provider);
     }
 
+    // https://github.com/SixLabors/ImageSharp/issues/2469
+    [Theory]
+    [WithFile(TestImages.Png.Issue2668, PixelTypes.Rgba32)]
+    public void Issue2668_Quantized_Encode_Alpha<TPixel>(TestImageProvider<TPixel> provider)
+        where TPixel : unmanaged, IPixel<TPixel>
+    {
+        using Image<TPixel> image = provider.GetImage(PngDecoder.Instance);
+        image.Mutate(x => x.Resize(100, 100));
+
+        PngEncoder encoder = new() { BitDepth = PngBitDepth.Bit8, ColorType = PngColorType.Palette };
+
+        string actualOutputFile = provider.Utility.SaveTestOutputFile(image, "png", encoder);
+        using Image<Rgba32> encoded = Image.Load<Rgba32>(actualOutputFile);
+        encoded.CompareToReferenceOutput(ImageComparer.Exact, provider);
+    }
+
     private static void TestPngEncoderCore<TPixel>(
         TestImageProvider<TPixel> provider,
         PngColorType pngColorType,
diff --git a/tests/ImageSharp.Tests/TestImages.cs b/tests/ImageSharp.Tests/TestImages.cs
index 4e33bbd8ad..3d9da1072a 100644
--- a/tests/ImageSharp.Tests/TestImages.cs
+++ b/tests/ImageSharp.Tests/TestImages.cs
@@ -151,6 +151,9 @@ public static class Png
         // Issue 2447: https://github.com/SixLabors/ImageSharp/issues/2447
         public const string Issue2447 = "Png/issues/issue_2447.png";
 
+        // Issue 2668: https://github.com/SixLabors/ImageSharp/issues/2668
+        public const string Issue2668 = "Png/issues/Issue_2668.png";
+
         public static class Bad
         {
             public const string MissingDataChunk = "Png/xdtn0g01.png";
diff --git a/tests/Images/External/ReferenceOutput/PngEncoderTests/Issue2668_Quantized_Encode_Alpha_Rgba32_Issue_2668.png b/tests/Images/External/ReferenceOutput/PngEncoderTests/Issue2668_Quantized_Encode_Alpha_Rgba32_Issue_2668.png
new file mode 100644
index 0000000000..7af5391f70
--- /dev/null
+++ b/tests/Images/External/ReferenceOutput/PngEncoderTests/Issue2668_Quantized_Encode_Alpha_Rgba32_Issue_2668.png
@@ -0,0 +1,3 @@
+version https://git-lfs.github.com/spec/v1
+oid sha256:f934af128b85b9e8f557d71ac8b1f1473a0922d0754fc0c4ece0d0e3d8d94c39
+size 7702
diff --git a/tests/Images/Input/Png/issues/Issue_2668.png b/tests/Images/Input/Png/issues/Issue_2668.png
new file mode 100644
index 0000000000..2ca8c46171
--- /dev/null
+++ b/tests/Images/Input/Png/issues/Issue_2668.png
@@ -0,0 +1,3 @@
+version https://git-lfs.github.com/spec/v1
+oid sha256:e8e5b2b933fd8fefd161f1d22970cb60247fd2d93b6c07b8b9ee1fdbc2241a3c
+size 390225