diff --git a/CHANGELOG.md b/CHANGELOG.md
index 37ad1a59cc60..5395c16dc489 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -16,6 +16,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - Ensure `-outline-offset-*` utilities are suggested in IntelliSense ([#15646](https://github.com/tailwindlabs/tailwindcss/pull/15646))
 - Write to `stdout` when `--output` is set to `-` or omitted for `@tailwindcss/cli` ([#15656](https://github.com/tailwindlabs/tailwindcss/pull/15656))
 - Write to `stdout` when `--output -` flag is used for `@tailwindcss/cli` ([#15656](https://github.com/tailwindlabs/tailwindcss/pull/15656))
+- Prevent `not-*` from being used with variants that have multiple sibling rules ([#15689](https://github.com/tailwindlabs/tailwindcss/pull/15689))
 - _Upgrade (experimental)_: Pretty print `--spacing(…)` to prevent ambiguity ([#15596](https://github.com/tailwindlabs/tailwindcss/pull/15596))
 
 ### Changed
diff --git a/packages/tailwindcss/src/compile.ts b/packages/tailwindcss/src/compile.ts
index 2275971fb71e..5d7e82f73d03 100644
--- a/packages/tailwindcss/src/compile.ts
+++ b/packages/tailwindcss/src/compile.ts
@@ -219,6 +219,15 @@ export function applyVariant(
     let result = applyVariant(isolatedNode, variant.variant, variants, depth + 1)
     if (result === null) return null
 
+    if (variant.root === 'not' && isolatedNode.nodes.length > 1) {
+      // The `not` variant cannot negate sibling rules / at-rules because these
+      // are an OR relationship. Doing so would require transforming sibling
+      // nodes into nesting while negating them. This isn't possible with the
+      // current implementation of the `not` variant or with how variants are
+      // applied in general (on a per-node basis).
+      return null
+    }
+
     for (let child of isolatedNode.nodes) {
       // Only some variants wrap children in rules. For example, the `force`
       // variant is a noop on the AST. And the `has` variant modifies the
diff --git a/packages/tailwindcss/src/variants.test.ts b/packages/tailwindcss/src/variants.test.ts
index 5f4b9d106aa2..e70970a92bed 100644
--- a/packages/tailwindcss/src/variants.test.ts
+++ b/packages/tailwindcss/src/variants.test.ts
@@ -1644,6 +1644,30 @@ test('not', async () => {
             }
           }
         }
+        @custom-variant parallel-style-rules {
+          &:hover {
+            @slot;
+          }
+          &:focus {
+            @slot;
+          }
+        }
+        @custom-variant parallel-at-rules {
+          @media foo {
+            @slot;
+          }
+          @media bar {
+            @slot;
+          }
+        }
+        @custom-variant parallel-mixed-rules {
+          &:hover {
+            @slot;
+          }
+          @media bar {
+            @slot;
+          }
+        }
         @tailwind utilities;
       `,
       [
@@ -1660,23 +1684,27 @@ test('not', async () => {
         'not-multiple-media-conditions:flex',
         'not-starting:flex',
 
+        'not-parallel-style-rules:flex',
+        'not-parallel-at-rules:flex',
+        'not-parallel-mixed-rules:flex',
+
         // The following built-in variants don't have not-* versions because
         // there is no sensible negative version of them.
 
         // These just don't make sense as not-*
-        'not-force',
-        'not-*',
+        'not-force:flex',
+        'not-*:flex',
 
         // These contain pseudo-elements
-        'not-first-letter',
-        'not-first-line',
-        'not-marker',
-        'not-selection',
-        'not-file',
-        'not-placeholder',
-        'not-backdrop',
-        'not-before',
-        'not-after',
+        'not-first-letter:flex',
+        'not-first-line:flex',
+        'not-marker:flex',
+        'not-selection:flex',
+        'not-file:flex',
+        'not-placeholder:flex',
+        'not-backdrop:flex',
+        'not-before:flex',
+        'not-after:flex',
 
         // This is not a conditional at rule
         'not-starting:flex',