diff --git a/lib/handler/cache-handler.js b/lib/handler/cache-handler.js
index 6e13f8eb17c..ba5584b4b5e 100644
--- a/lib/handler/cache-handler.js
+++ b/lib/handler/cache-handler.js
@@ -118,6 +118,7 @@ class CacheHandler {
       } catch {
         // Fail silently
       }
+      this.#deleteLocationHeaderEntries(resHeaders)
       return downstreamOnHeaders()
     }
 
@@ -314,6 +315,58 @@ class CacheHandler {
     }
   }
 
+  /**
+   * Deletes the cache entries for the URIs in the response's Location and
+   * Content-Location headers when they share the request URI's origin
+   *  https://www.rfc-editor.org/rfc/rfc9111.html#section-4.4
+   *
+   * @param {import('../../types/header.d.ts').IncomingHttpHeaders} resHeaders
+   */
+  #deleteLocationHeaderEntries (resHeaders) {
+    let requestUrl
+    try {
+      requestUrl = new URL(this.#cacheKey.path, this.#cacheKey.origin)
+    } catch {
+      // Can't resolve the request URI, don't invalidate anything else
+      return
+    }
+
+    const invalidatedPaths = new Set([this.#cacheKey.path])
+
+    for (const headerName of ['location', 'content-location']) {
+      const header = resHeaders[headerName]
+      const value = Array.isArray(header) ? header[0] : header
+      if (typeof value !== 'string' || value === '') {
+        continue
+      }
+
+      let url
+      try {
+        url = new URL(value, requestUrl)
+      } catch {
+        continue
+      }
+
+      if (url.origin !== requestUrl.origin) {
+        // Only invalidate URIs sharing the request URI's origin, invalidating
+        //  cross-origin URIs could be used for cache poisoning
+        continue
+      }
+
+      const path = `${url.pathname}${url.search}`
+      if (invalidatedPaths.has(path)) {
+        continue
+      }
+      invalidatedPaths.add(path)
+
+      try {
+        this.#store.delete({ ...this.#cacheKey, path })?.catch?.(noop)
+      } catch {
+        // Fail silently
+      }
+    }
+  }
+
   onResponseData (controller, chunk) {
     if (this.#writeStream?.write(chunk) === false) {
       controller.pause()
diff --git a/test/interceptors/cache.js b/test/interceptors/cache.js
index e31b1e307d0..2ed7b650f78 100644
--- a/test/interceptors/cache.js
+++ b/test/interceptors/cache.js
@@ -531,6 +531,83 @@ describe('Cache Interceptor', () => {
     }
   })
 
+  test('unsafe methods invalidate the URIs in Location and Content-Location response headers', async () => {
+    const requestsToOrigin = {
+      '/target': 0,
+      '/content-target': 0,
+      '/cross-origin-target': 0
+    }
+
+    const server = createServer({ joinDuplicateHeaders: true }, (req, res) => {
+      if (req.method === 'GET') {
+        requestsToOrigin[req.url]++
+        res.setHeader('cache-control', 'public, s-maxage=100')
+        res.end('asd')
+        return
+      }
+
+      res.statusCode = 204
+      if (req.url === '/same-origin') {
+        // Absolute same-origin Location, relative Content-Location
+        res.setHeader('location', `http://localhost:${server.address().port}/target`)
+        res.setHeader('content-location', '/content-target')
+      } else if (req.url === '/cross-origin') {
+        // Same path as a cached entry but a different origin, must not be
+        //  invalidated
+        res.setHeader('location', 'http://other-origin.example/cross-origin-target')
+      }
+      res.end()
+    }).listen(0)
+
+    const client = new Client(`http://localhost:${server.address().port}`)
+      .compose(interceptors.cache())
+
+    after(async () => {
+      server.close()
+      await client.close()
+    })
+
+    await once(server, 'listening')
+
+    const origin = `http://localhost:${server.address().port}`
+
+    // Prime the cache and make sure the responses are served from it
+    for (const path of Object.keys(requestsToOrigin)) {
+      for (let i = 0; i < 2; i++) {
+        const res = await client.request({ origin, method: 'GET', path })
+        strictEqual(await res.body.text(), 'asd')
+        equal(requestsToOrigin[path], 1, path)
+      }
+    }
+
+    // Successful unsafe request whose response points at /target and
+    //  /content-target, both must be invalidated
+    //  https://www.rfc-editor.org/rfc/rfc9111.html#section-4.4
+    {
+      const res = await client.request({ origin, method: 'POST', path: '/same-origin' })
+      await res.body.text()
+    }
+
+    for (const path of ['/target', '/content-target']) {
+      const res = await client.request({ origin, method: 'GET', path })
+      strictEqual(await res.body.text(), 'asd')
+      equal(requestsToOrigin[path], 2, path)
+    }
+
+    // Successful unsafe request whose response Location shares a path with a
+    //  cached entry but sits on another origin, the cached entry must survive
+    {
+      const res = await client.request({ origin, method: 'POST', path: '/cross-origin' })
+      await res.body.text()
+    }
+
+    {
+      const res = await client.request({ origin, method: 'GET', path: '/cross-origin-target' })
+      strictEqual(await res.body.text(), 'asd')
+      equal(requestsToOrigin['/cross-origin-target'], 1)
+    }
+  })
+
   test('unsafe methods aren\'t cached', async () => {
     const server = createServer({ joinDuplicateHeaders: true }, (_, res) => {
       res.setHeader('cache-control', 'public, s-maxage=1')