diff --git a/src/libraries/System.Private.CoreLib/src/System/MemoryExtensions.cs b/src/libraries/System.Private.CoreLib/src/System/MemoryExtensions.cs
index ce3f24f7d6513d..658a464d6d3d2d 100644
--- a/src/libraries/System.Private.CoreLib/src/System/MemoryExtensions.cs
+++ b/src/libraries/System.Private.CoreLib/src/System/MemoryExtensions.cs
@@ -592,6 +592,67 @@ public static int IndexOfAnyExcept<T>(this ReadOnlySpan<T> span, T value0, T val
             return -1;
         }
 
+        [MethodImpl(MethodImplOptions.AggressiveInlining)]
+        internal static int IndexOfAnyExcept<T>(this ReadOnlySpan<T> span, T value0, T value1, T value2, T value3) where T : IEquatable<T>?
+        {
+            if (RuntimeHelpers.IsBitwiseEquatable<T>())
+            {
+                if (Unsafe.SizeOf<T>() == sizeof(byte))
+                {
+                    return SpanHelpers.IndexOfAnyExceptValueType(
+                        ref Unsafe.As<T, byte>(ref MemoryMarshal.GetReference(span)),
+                        Unsafe.As<T, byte>(ref value0),
+                        Unsafe.As<T, byte>(ref value1),
+                        Unsafe.As<T, byte>(ref value2),
+                        Unsafe.As<T, byte>(ref value3),
+                        span.Length);
+                }
+                else if (Unsafe.SizeOf<T>() == sizeof(short))
+                {
+                    return SpanHelpers.IndexOfAnyExceptValueType(
+                        ref Unsafe.As<T, short>(ref MemoryMarshal.GetReference(span)),
+                        Unsafe.As<T, short>(ref value0),
+                        Unsafe.As<T, short>(ref value1),
+                        Unsafe.As<T, short>(ref value2),
+                        Unsafe.As<T, short>(ref value3),
+                        span.Length);
+                }
+                else if (Unsafe.SizeOf<T>() == sizeof(int))
+                {
+                    return SpanHelpers.IndexOfAnyExceptValueType(
+                        ref Unsafe.As<T, int>(ref MemoryMarshal.GetReference(span)),
+                        Unsafe.As<T, int>(ref value0),
+                        Unsafe.As<T, int>(ref value1),
+                        Unsafe.As<T, int>(ref value2),
+                        Unsafe.As<T, int>(ref value3),
+                        span.Length);
+                }
+                else if (Unsafe.SizeOf<T>() == sizeof(long))
+                {
+                    return SpanHelpers.IndexOfAnyExceptValueType(
+                        ref Unsafe.As<T, long>(ref MemoryMarshal.GetReference(span)),
+                        Unsafe.As<T, long>(ref value0),
+                        Unsafe.As<T, long>(ref value1),
+                        Unsafe.As<T, long>(ref value2),
+                        Unsafe.As<T, long>(ref value3),
+                        span.Length);
+                }
+            }
+
+            for (int i = 0; i < span.Length; i++)
+            {
+                if (!EqualityComparer<T>.Default.Equals(span[i], value0) &&
+                    !EqualityComparer<T>.Default.Equals(span[i], value1) &&
+                    !EqualityComparer<T>.Default.Equals(span[i], value2) &&
+                    !EqualityComparer<T>.Default.Equals(span[i], value3))
+                {
+                    return i;
+                }
+            }
+
+            return -1;
+        }
+
         /// <summary>Searches for the first index of any value other than the specified <paramref name="values"/>.</summary>
         /// <typeparam name="T">The type of the span and values.</typeparam>
         /// <param name="span">The span to search.</param>
@@ -619,6 +680,9 @@ public static int IndexOfAnyExcept<T>(this ReadOnlySpan<T> span, ReadOnlySpan<T>
                 case 3:
                     return IndexOfAnyExcept(span, values[0], values[1], values[2]);
 
+                case 4: // common for searching whitespaces
+                    return IndexOfAnyExcept(span, values[0], values[1], values[2], values[3]);
+
                 default:
                     for (int i = 0; i < span.Length; i++)
                     {
diff --git a/src/libraries/System.Private.CoreLib/src/System/SpanHelpers.T.cs b/src/libraries/System.Private.CoreLib/src/System/SpanHelpers.T.cs
index ed26ed9d04958b..709a423680af0f 100644
--- a/src/libraries/System.Private.CoreLib/src/System/SpanHelpers.T.cs
+++ b/src/libraries/System.Private.CoreLib/src/System/SpanHelpers.T.cs
@@ -1220,19 +1220,72 @@ public static int IndexOfAnyExceptValueType<T>(ref T searchSpace, T value0, int
                         return ComputeIndex(ref searchSpace, ref oneVectorAwayFromEnd, notEquals);
                     }
                 }
+            }
+
+            return -1;
+        }
+
+        internal static int IndexOfAnyExceptValueType<T>(ref T searchSpace, T value0, T value1, T value2, T value3, int length) where T : struct, IEquatable<T>
+        {
+            Debug.Assert(length >= 0, "Expected non-negative length");
+            Debug.Assert(value0 is byte or short or int or long, "Expected caller to normalize to one of these types");
 
-                [MethodImpl(MethodImplOptions.AggressiveInlining)]
-                static int ComputeIndex(ref T searchSpace, ref T current, Vector128<T> notEquals)
+            if (!Vector128.IsHardwareAccelerated || length < Vector128<T>.Count)
+            {
+                for (int i = 0; i < length; i++)
                 {
-                    uint notEqualsElements = notEquals.ExtractMostSignificantBits();
-                    int index = BitOperations.TrailingZeroCount(notEqualsElements);
-                    return index + (int)(Unsafe.ByteOffset(ref searchSpace, ref current) / Unsafe.SizeOf<T>());
+                    T current = Unsafe.Add(ref searchSpace, i);
+                    if (!current.Equals(value0) && !current.Equals(value1) && !current.Equals(value2) && !current.Equals(value3))
+                    {
+                        return i;
+                    }
+                }
+            }
+            else
+            {
+                Vector128<T> notEquals, current, values0 = Vector128.Create(value0), values1 = Vector128.Create(value1), values2 = Vector128.Create(value2), values3 = Vector128.Create(value3);
+                ref T currentSearchSpace = ref searchSpace;
+                ref T oneVectorAwayFromEnd = ref Unsafe.Add(ref searchSpace, length - Vector128<T>.Count);
+
+                // Loop until either we've finished all elements or there's less than a vector's-worth remaining.
+                do
+                {
+                    current = Vector128.LoadUnsafe(ref currentSearchSpace);
+                    notEquals = ~(Vector128.Equals(values0, current) | Vector128.Equals(values1, current)
+                                | Vector128.Equals(values2, current) | Vector128.Equals(values3, current));
+                    if (notEquals != Vector128<T>.Zero)
+                    {
+                        return ComputeIndex(ref searchSpace, ref currentSearchSpace, notEquals);
+                    }
+
+                    currentSearchSpace = ref Unsafe.Add(ref currentSearchSpace, Vector128<T>.Count);
+                }
+                while (!Unsafe.IsAddressGreaterThan(ref currentSearchSpace, ref oneVectorAwayFromEnd));
+
+                // If any elements remain, process the last vector in the search space.
+                if ((uint)length % Vector128<T>.Count != 0)
+                {
+                    current = Vector128.LoadUnsafe(ref oneVectorAwayFromEnd);
+                    notEquals = ~(Vector128.Equals(values0, current) | Vector128.Equals(values1, current)
+                                | Vector128.Equals(values2, current) | Vector128.Equals(values3, current));
+                    if (notEquals != Vector128<T>.Zero)
+                    {
+                        return ComputeIndex(ref searchSpace, ref oneVectorAwayFromEnd, notEquals);
+                    }
                 }
             }
 
             return -1;
         }
 
+        [MethodImpl(MethodImplOptions.AggressiveInlining)]
+        private static int ComputeIndex<T>(ref T searchSpace, ref T current, Vector128<T> notEquals) where T : struct, IEquatable<T>
+        {
+            uint notEqualsElements = notEquals.ExtractMostSignificantBits();
+            int index = BitOperations.TrailingZeroCount(notEqualsElements);
+            return index + (int)(Unsafe.ByteOffset(ref searchSpace, ref current) / Unsafe.SizeOf<T>());
+        }
+
         public static bool SequenceEqual<T>(ref T first, ref T second, int length) where T : IEquatable<T>?
         {
             Debug.Assert(length >= 0);