diff --git a/browser/net/BUILD.gn b/browser/net/BUILD.gn
index 23fd8c5be7ce..5e2772fee93e 100644
--- a/browser/net/BUILD.gn
+++ b/browser/net/BUILD.gn
@@ -63,6 +63,7 @@ source_set("net") {
     "//brave/extensions:common",
     "//components/content_settings/core/browser",
     "//components/prefs",
+    "//components/proxy_config",
     "//components/user_prefs",
     "//content/public/browser",
     "//content/public/common",
diff --git a/browser/net/brave_ad_block_tp_network_delegate_helper.cc b/browser/net/brave_ad_block_tp_network_delegate_helper.cc
index 76d2253a7b06..33464a966b77 100644
--- a/browser/net/brave_ad_block_tp_network_delegate_helper.cc
+++ b/browser/net/brave_ad_block_tp_network_delegate_helper.cc
@@ -22,8 +22,12 @@
 #include "brave/components/brave_shields/common/brave_shield_constants.h"
 #include "brave/components/brave_shields/common/features.h"
 #include "brave/grit/brave_generated_resources.h"
+#include "chrome/browser/net/proxy_service_factory.h"
 #include "chrome/browser/net/secure_dns_config.h"
 #include "chrome/browser/net/system_network_context_manager.h"
+#include "chrome/browser/profiles/profile.h"
+#include "components/prefs/pref_service.h"
+#include "components/proxy_config/pref_proxy_config_tracker.h"
 #include "content/public/browser/browser_context.h"
 #include "content/public/browser/browser_thread.h"
 #include "content/public/browser/render_frame_host.h"
@@ -32,6 +36,9 @@
 #include "content/public/common/url_constants.h"
 #include "extensions/common/url_pattern.h"
 #include "mojo/public/cpp/bindings/remote.h"
+#include "net/proxy_resolution/proxy_config.h"
+#include "net/proxy_resolution/proxy_config_service.h"
+#include "net/proxy_resolution/proxy_config_with_annotation.h"
 #include "services/network/host_resolver.h"
 #include "services/network/network_context.h"
 #include "ui/base/resource/resource_bundle.h"
@@ -228,6 +235,41 @@ void UseCnameResult(scoped_refptr<base::SequencedTaskRunner> task_runner,
   }
 }
 
+// If only particular types of network traffic are being proxied, or if no
+// proxy is configured, it should be safe to continue making unproxied DNS
+// queries. However, in SingleProxy mode all types of network traffic should go
+// through the proxy, so additional DNS queries should be avoided.
+bool ProxySettingsAllowUncloaking(content::BrowserContext* browser_context) {
+  DCHECK(browser_context);
+
+  bool can_uncloak = true;
+
+  Profile* profile = Profile::FromBrowserContext(browser_context);
+
+  std::unique_ptr<PrefProxyConfigTracker> config_tracker =
+      ProxyServiceFactory::CreatePrefProxyConfigTrackerOfProfile(
+          profile->GetPrefs(), nullptr);
+  std::unique_ptr<net::ProxyConfigService> proxy_config_service =
+      ProxyServiceFactory::CreateProxyConfigService(config_tracker.get());
+
+  net::ProxyConfigWithAnnotation config;
+  net::ProxyConfigService::ConfigAvailability availability =
+      proxy_config_service->GetLatestProxyConfig(&config);
+
+  if (availability ==
+      net::ProxyConfigService::ConfigAvailability::CONFIG_VALID) {
+    // PROXY_LIST corresponds to SingleProxy mode.
+    if (config.value().proxy_rules().type ==
+        net::ProxyConfig::ProxyRules::Type::PROXY_LIST) {
+      can_uncloak = false;
+    }
+  }
+
+  config_tracker->DetachFromPrefService();
+
+  return can_uncloak;
+}
+
 void OnBeforeURLRequestAdBlockTP(const ResponseCallback& next_callback,
                                  std::shared_ptr<BraveRequestInfo> ctx) {
   DCHECK_CURRENTLY_ON(content::BrowserThread::UI);
@@ -240,10 +282,12 @@ void OnBeforeURLRequestAdBlockTP(const ResponseCallback& next_callback,
 
   // DoH or standard DNS queries won't be routed through Tor, so we need to
   // skip it.
+  // Also, skip CNAME uncloaking if there is currently a configured proxy.
   bool should_check_uncloaked =
       base::FeatureList::IsEnabled(
           brave_shields::features::kBraveAdblockCnameUncloaking) &&
-      ctx->browser_context && !ctx->browser_context->IsTor();
+      ctx->browser_context && !ctx->browser_context->IsTor() &&
+      ProxySettingsAllowUncloaking(ctx->browser_context);
 
   task_runner->PostTaskAndReplyWithResult(
       FROM_HERE,