diff --git a/extensions/resteasy-reactive/rest-client-reactive/deployment/src/test/java/io/quarkus/rest/client/reactive/InvalidHostTest.java b/extensions/resteasy-reactive/rest-client-reactive/deployment/src/test/java/io/quarkus/rest/client/reactive/InvalidHostTest.java
new file mode 100644
index 0000000000000..88b25b6b104e6
--- /dev/null
+++ b/extensions/resteasy-reactive/rest-client-reactive/deployment/src/test/java/io/quarkus/rest/client/reactive/InvalidHostTest.java
@@ -0,0 +1,53 @@
+package io.quarkus.rest.client.reactive;
+
+import java.net.URI;
+
+import javax.ws.rs.GET;
+import javax.ws.rs.Path;
+import javax.ws.rs.core.MultivaluedMap;
+import javax.ws.rs.core.Response;
+
+import org.assertj.core.api.Assertions;
+import org.eclipse.microprofile.rest.client.RestClientBuilder;
+import org.eclipse.microprofile.rest.client.ext.ResponseExceptionMapper;
+import org.junit.jupiter.api.Test;
+import org.junit.jupiter.api.extension.RegisterExtension;
+
+import io.quarkus.test.QuarkusUnitTest;
+
+public class InvalidHostTest {
+
+    @RegisterExtension
+    static final QuarkusUnitTest TEST = new QuarkusUnitTest();
+
+    @Test
+    void shouldThrowDummyException() {
+        Client client = RestClientBuilder.newBuilder().baseUri(URI.create("http://localhost2:1234/"))
+                .register(DummyExceptionMapper.class).build(Client.class);
+
+        Assertions.assertThatThrownBy(client::get).isInstanceOf(DummyException.class);
+    }
+
+    @Path("/foo")
+    public interface Client {
+        @GET
+        String get();
+    }
+
+    public static class DummyException extends RuntimeException {
+
+    }
+
+    public static class DummyExceptionMapper implements ResponseExceptionMapper<DummyException> {
+
+        @Override
+        public boolean handles(int status, MultivaluedMap<String, Object> headers) {
+            return status == 0 && headers.isEmpty();
+        }
+
+        @Override
+        public DummyException toThrowable(Response response) {
+            return new DummyException();
+        }
+    }
+}
diff --git a/independent-projects/resteasy-reactive/client/runtime/src/main/java/org/jboss/resteasy/reactive/client/handlers/ClientSendRequestHandler.java b/independent-projects/resteasy-reactive/client/runtime/src/main/java/org/jboss/resteasy/reactive/client/handlers/ClientSendRequestHandler.java
index cd26798627e55..753cc79d73574 100644
--- a/independent-projects/resteasy-reactive/client/runtime/src/main/java/org/jboss/resteasy/reactive/client/handlers/ClientSendRequestHandler.java
+++ b/independent-projects/resteasy-reactive/client/runtime/src/main/java/org/jboss/resteasy/reactive/client/handlers/ClientSendRequestHandler.java
@@ -51,6 +51,7 @@
 import org.jboss.resteasy.reactive.client.spi.ClientRestHandler;
 import org.jboss.resteasy.reactive.client.spi.MultipartResponseData;
 import org.jboss.resteasy.reactive.common.core.Serialisers;
+import org.jboss.resteasy.reactive.common.util.MultivaluedTreeMap;
 
 public class ClientSendRequestHandler implements ClientRestHandler {
     private static final Logger log = Logger.getLogger(ClientSendRequestHandler.class);
@@ -247,6 +248,10 @@ public void handle(Throwable failure) {
         }, new Consumer<>() {
             @Override
             public void accept(Throwable event) {
+                // set some properties to prevent NPEs down the chain
+                requestContext.setResponseHeaders(new MultivaluedTreeMap<>());
+                requestContext.setResponseReasonPhrase("unknown");
+
                 if (event instanceof IOException) {
                     ProcessingException throwable = new ProcessingException(event);
                     reportFinish(throwable, requestContext);