diff --git a/packages/cli/src/lib/db/regions.ts b/packages/cli/src/lib/db/regions.ts
index 4fa60b2ab..43c9d9868 100644
--- a/packages/cli/src/lib/db/regions.ts
+++ b/packages/cli/src/lib/db/regions.ts
@@ -268,8 +268,33 @@ export function getOrgRegion(
     | Pick<OrgRegionRow, "region_url">
     | undefined;
 
-  recordCacheHit("region", !!row);
-  return row?.region_url;
+  const regionUrl = usableRegionUrl(row?.region_url, orgSlug);
+  recordCacheHit("region", !!regionUrl);
+  return regionUrl;
+}
+
+/**
+ * Reject cached region URLs that are not absolute HTTP(S) URLs.
+ *
+ * Older CLI releases persisted a self-hosted org's raw `links.regionUrl`
+ * (e.g. "" or "/"). Returning such a value makes SDK requests use a bare
+ * path like `/api/0/...`, which `new Request()` rejects (CLI-2DE). Treating
+ * it as a cache miss forces a fresh lookup that resolves an absolute URL.
+ */
+function usableRegionUrl(
+  regionUrl: string | undefined,
+  orgSlug: string,
+): string | undefined {
+  if (!regionUrl) {
+    return;
+  }
+  if (!normalizeHttpOrigin(regionUrl)) {
+    log.debug(
+      `Ignoring cached non-absolute region URL for '${orgSlug}': '${regionUrl}'`,
+    );
+    return;
+  }
+  return regionUrl;
 }
 
 /**
@@ -299,10 +324,11 @@ export function getOrgByNumericId(
     | Pick<OrgRegionRow, "org_slug" | "region_url">
     | undefined;
 
-  if (!row) {
+  const regionUrl = usableRegionUrl(row?.region_url, row?.org_slug ?? "");
+  if (!(row && regionUrl)) {
     return;
   }
-  return { slug: row.org_slug, regionUrl: row.region_url };
+  return { slug: row.org_slug, regionUrl };
 }
 
 /**
diff --git a/packages/cli/src/lib/sentry-client.ts b/packages/cli/src/lib/sentry-client.ts
index ac25222c3..3382feb7b 100644
--- a/packages/cli/src/lib/sentry-client.ts
+++ b/packages/cli/src/lib/sentry-client.ts
@@ -39,6 +39,7 @@ import {
 } from "./db/auth.js";
 import {
   ApiError,
+  ConfigError,
   HostScopeError,
   MalformedAuthTokenError,
   TimeoutError,
@@ -1118,6 +1119,15 @@ export function getSdkConfig(
     ? regionUrl.slice(0, -1)
     : regionUrl;
 
+  // A relative/empty base makes SDK requests use a bare `/api/0/...` path,
+  // which undici rejects with an opaque "Failed to parse URL" (CLI-2DE).
+  if (!normalizeHttpOrigin(normalizedBase)) {
+    throw new ConfigError(
+      `Invalid Sentry API base URL: '${regionUrl}' is not an absolute HTTP(S) URL.`,
+      "Set SENTRY_URL to your Sentry instance (e.g. https://sentry.example.com) and retry.",
+    );
+  }
+
   return {
     // SDK functions already include /api/0/ in their URL paths,
     // so baseUrl should be the plain region URL without /api/0.
diff --git a/packages/cli/test/lib/db/regions.focused.test.ts b/packages/cli/test/lib/db/regions.focused.test.ts
index c90e392ad..ba1e58de1 100644
--- a/packages/cli/test/lib/db/regions.focused.test.ts
+++ b/packages/cli/test/lib/db/regions.focused.test.ts
@@ -1,5 +1,7 @@
 import { describe, expect, test } from "vitest";
+import { getDatabase } from "../../../src/lib/db/index.js";
 import {
+  getOrgByNumericId,
   getOrgRegion,
   isTrustedRegionOrigin,
   resetTrustedRegionUrlsForTesting,
@@ -62,4 +64,17 @@ describe("credential and origin scoped organization regions", () => {
       setOrgRegion("invalid", regionUrl, SOURCE_A, SOURCE_A, IDENTITY_A),
     ).toThrow();
   });
+
+  test.each(["", "/", "/sentry"])(
+    "treats a legacy non-absolute cached region URL %j as a cache miss (CLI-2DE)",
+    (regionUrl) => {
+      getDatabase()
+        .query(
+          "INSERT INTO org_regions (org_slug, org_id, region_url, credential_identity, source_origin, response_origin, updated_at) VALUES (?, ?, ?, ?, ?, ?, ?)",
+        )
+        .run("legacy", "4242", regionUrl, IDENTITY_A, SOURCE_A, SOURCE_A, 0);
+      expect(getOrgRegion("legacy", SOURCE_A, IDENTITY_A)).toBeUndefined();
+      expect(getOrgByNumericId("4242", SOURCE_A, IDENTITY_A)).toBeUndefined();
+    },
+  );
 });
diff --git a/packages/cli/test/lib/region.test.ts b/packages/cli/test/lib/region.test.ts
index 8332d75d0..828fa446f 100644
--- a/packages/cli/test/lib/region.test.ts
+++ b/packages/cli/test/lib/region.test.ts
@@ -240,6 +240,40 @@ describe("resolveOrgRegion", () => {
     }
   });
 
+  test("falls back to baseUrl when API returns an empty regionUrl (CLI-2DE)", async () => {
+    const originalFetch = globalThis.fetch;
+    globalThis.fetch = async (input: RequestInfo | URL, init?: RequestInit) => {
+      const req = new Request(input, init);
+      if (req.url.includes("/organizations/empty-region-org/")) {
+        return new Response(
+          JSON.stringify({
+            id: "791",
+            slug: "empty-region-org",
+            name: "Self-hosted Org 3",
+            links: {
+              organizationUrl: "/organizations/empty-region-org/",
+              regionUrl: "",
+            },
+          }),
+          {
+            status: 200,
+            headers: { "Content-Type": "application/json" },
+          },
+        );
+      }
+      return new Response(JSON.stringify({ detail: "Not found" }), {
+        status: 404,
+      });
+    };
+
+    try {
+      const regionUrl = await resolveOrgRegion("empty-region-org");
+      expect(regionUrl).toBe("https://sentry.io");
+    } finally {
+      globalThis.fetch = originalFetch;
+    }
+  });
+
   test("falls back to baseUrl when API returns a malformed regionUrl", async () => {
     const originalFetch = globalThis.fetch;
     globalThis.fetch = async (input: RequestInfo | URL, init?: RequestInit) => {
diff --git a/packages/cli/test/lib/sentry-client.test.ts b/packages/cli/test/lib/sentry-client.test.ts
index 89df80c7d..b7ea7c07a 100644
--- a/packages/cli/test/lib/sentry-client.test.ts
+++ b/packages/cli/test/lib/sentry-client.test.ts
@@ -5,7 +5,7 @@
 
 import { afterEach, beforeEach, describe, expect, test } from "vitest";
 import { setAuthToken } from "../../src/lib/db/auth.js";
-import { TimeoutError } from "../../src/lib/errors.js";
+import { ConfigError, TimeoutError } from "../../src/lib/errors.js";
 import {
   __injectTimeoutOverrideForTests,
   __resolveRequestTimeoutMsForTests,
@@ -35,6 +35,19 @@ function getAuthenticatedFetch(): typeof fetch {
   return getSdkConfig(REGION_URL).fetch as typeof fetch;
 }
 
+describe("getSdkConfig base URL validation", () => {
+  test.each(["", "/", "/sentry/"])(
+    "rejects non-absolute base URL %j with ConfigError (CLI-2DE)",
+    (base) => {
+      expect(() => getSdkConfig(base)).toThrow(ConfigError);
+    },
+  );
+
+  test("strips a trailing slash from an absolute base URL", () => {
+    expect(getSdkConfig(`${REGION_URL}/`).baseUrl).toBe(REGION_URL);
+  });
+});
+
 describe("fetchWithRetry / buildAttemptFactory", () => {
   test("retries a POST with a string body without re-consuming the body", async () => {
     const marker = "__test_string_body__";