diff --git a/core/deployment/src/main/java/io/quarkus/deployment/steps/ApplicationIndexBuildStep.java b/core/deployment/src/main/java/io/quarkus/deployment/steps/ApplicationIndexBuildStep.java
index 151a73cfe28540..52363375b5c4c2 100644
--- a/core/deployment/src/main/java/io/quarkus/deployment/steps/ApplicationIndexBuildStep.java
+++ b/core/deployment/src/main/java/io/quarkus/deployment/steps/ApplicationIndexBuildStep.java
@@ -7,6 +7,8 @@
 import java.nio.file.Files;
 import java.nio.file.Path;
 import java.nio.file.attribute.BasicFileAttributes;
+import java.util.Collections;
+import java.util.Set;
 
 import org.jboss.jandex.Index;
 import org.jboss.jandex.Indexer;
@@ -15,14 +17,19 @@
 import io.quarkus.deployment.annotations.BuildStep;
 import io.quarkus.deployment.builditem.ApplicationIndexBuildItem;
 import io.quarkus.deployment.builditem.ArchiveRootBuildItem;
+import io.quarkus.deployment.configuration.ClassLoadingConfig;
+import io.quarkus.deployment.pkg.builditem.CurateOutcomeBuildItem;
+import io.quarkus.maven.dependency.ResolvedDependency;
 
 public class ApplicationIndexBuildStep {
 
     private static final Logger log = Logger.getLogger(ApplicationIndexBuildStep.class);
 
     @BuildStep
-    ApplicationIndexBuildItem build(ArchiveRootBuildItem root) throws IOException {
+    ApplicationIndexBuildItem build(ArchiveRootBuildItem root, CurateOutcomeBuildItem curation,
+            ClassLoadingConfig classLoadingConfig) throws IOException {
         Indexer indexer = new Indexer();
+        Set<String> removedApplicationClasses = removedApplicationClasses(curation, classLoadingConfig);
         for (Path p : root.getRootDirectories()) {
             Files.walkFileTree(p, new FileVisitor<Path>() {
                 @Override
@@ -33,14 +40,33 @@ public FileVisitResult preVisitDirectory(Path dir, BasicFileAttributes attrs) th
                 @Override
                 public FileVisitResult visitFile(Path file, BasicFileAttributes attrs) throws IOException {
                     if (file.getFileName().toString().endsWith(".class")) {
-                        log.debugf("Indexing %s", file);
-                        try (InputStream stream = Files.newInputStream(file)) {
-                            indexer.index(stream);
+                        if (isRemovedApplicationClass(
+                                file.toString(), removedApplicationClasses)) {
+                            log.debugf("File %s will not be indexed because the class has been configured as part of '%s'",
+                                    file, "quarkus.class-loading.removed-resources");
+                        } else {
+                            log.debugf("Indexing %s", file);
+                            try (InputStream stream = Files.newInputStream(file)) {
+                                indexer.index(stream);
+                            }
                         }
                     }
                     return FileVisitResult.CONTINUE;
                 }
 
+                private boolean isRemovedApplicationClass(String fileName, Set<String> removedApplicationClasses) {
+                    if (removedApplicationClasses.isEmpty()) {
+                        return false;
+                    }
+                    String sanitizedFileName = (fileName.startsWith("/") ? fileName.substring(1) : fileName);
+                    for (String removedApplicationClass : removedApplicationClasses) {
+                        if (sanitizedFileName.endsWith(removedApplicationClass)) {
+                            return true;
+                        }
+                    }
+                    return false;
+                }
+
                 @Override
                 public FileVisitResult visitFileFailed(Path file, IOException exc) throws IOException {
                     return FileVisitResult.CONTINUE;
@@ -56,4 +82,11 @@ public FileVisitResult postVisitDirectory(Path dir, IOException exc) throws IOEx
         return new ApplicationIndexBuildItem(appIndex);
     }
 
+    private Set<String> removedApplicationClasses(CurateOutcomeBuildItem curation, ClassLoadingConfig classLoadingConfig) {
+        ResolvedDependency appArtifact = curation.getApplicationModel().getAppArtifact();
+        Set<String> entry = classLoadingConfig.removedResources
+                .get(appArtifact.getGroupId() + ":" + appArtifact.getArtifactId());
+        return entry != null ? entry : Collections.emptySet();
+    }
+
 }
diff --git a/core/deployment/src/main/java/io/quarkus/deployment/steps/ClassTransformingBuildStep.java b/core/deployment/src/main/java/io/quarkus/deployment/steps/ClassTransformingBuildStep.java
index c36fbdbbc4ce96..d9ab5a0d55fa6b 100644
--- a/core/deployment/src/main/java/io/quarkus/deployment/steps/ClassTransformingBuildStep.java
+++ b/core/deployment/src/main/java/io/quarkus/deployment/steps/ClassTransformingBuildStep.java
@@ -7,6 +7,7 @@
 import java.nio.file.Path;
 import java.nio.file.StandardOpenOption;
 import java.util.ArrayList;
+import java.util.Collection;
 import java.util.Collections;
 import java.util.HashMap;
 import java.util.HashSet;
@@ -32,6 +33,7 @@
 import io.quarkus.bootstrap.BootstrapDebug;
 import io.quarkus.bootstrap.classloading.ClassPathElement;
 import io.quarkus.bootstrap.classloading.QuarkusClassLoader;
+import io.quarkus.bootstrap.model.ApplicationModel;
 import io.quarkus.deployment.QuarkusClassVisitor;
 import io.quarkus.deployment.QuarkusClassWriter;
 import io.quarkus.deployment.annotations.BuildStep;
@@ -280,7 +282,12 @@ private void handleRemovedResources(ClassLoadingConfig classLoadingConfig, Curat
             removed.computeIfAbsent(i.getArtifact(), k -> new HashSet<>()).addAll(i.getResources());
         }
         if (!removed.isEmpty()) {
-            for (ResolvedDependency i : curateOutcomeBuildItem.getApplicationModel().getRuntimeDependencies()) {
+            ApplicationModel applicationModel = curateOutcomeBuildItem.getApplicationModel();
+            Collection<ResolvedDependency> runtimeDependencies = applicationModel.getRuntimeDependencies();
+            List<ResolvedDependency> allArtifacts = new ArrayList<>(runtimeDependencies.size() + 1);
+            allArtifacts.addAll(runtimeDependencies);
+            allArtifacts.add(applicationModel.getAppArtifact());
+            for (ResolvedDependency i : allArtifacts) {
                 Set<String> filtered = removed.remove(i.getKey());
                 if (filtered != null) {
                     for (Path path : i.getResolvedPaths()) {
diff --git a/integration-tests/main/src/main/java/io/quarkus/it/rest/RemovedJaxRsApplication.java b/integration-tests/main/src/main/java/io/quarkus/it/rest/RemovedJaxRsApplication.java
new file mode 100644
index 00000000000000..608a16672b605d
--- /dev/null
+++ b/integration-tests/main/src/main/java/io/quarkus/it/rest/RemovedJaxRsApplication.java
@@ -0,0 +1,11 @@
+package io.quarkus.it.rest;
+
+import javax.ws.rs.ApplicationPath;
+import javax.ws.rs.core.Application;
+
+/**
+ * This class is actually never used, because we configure Quarkus to remove it from Class Loading and build time indexing
+ */
+@ApplicationPath("unused")
+public class RemovedJaxRsApplication extends Application {
+}
diff --git a/integration-tests/main/src/main/resources/application.properties b/integration-tests/main/src/main/resources/application.properties
index 7631fcc4813c7b..a6e7df99951e96 100644
--- a/integration-tests/main/src/main/resources/application.properties
+++ b/integration-tests/main/src/main/resources/application.properties
@@ -53,4 +53,5 @@ quarkus.native.resources.excludes = **/unwanted.*
 quarkus.log.metrics.enabled=true
 
 quarkus.native.additional-build-args =-H:ReflectionConfigurationFiles=reflection-config.json
-quarkus.class-loading.removed-resources."io.quarkus\:quarkus-integration-test-shared-library"=io/quarkus/it/shared/RemovedResource.class
\ No newline at end of file
+quarkus.class-loading.removed-resources."io.quarkus\:quarkus-integration-test-shared-library"=io/quarkus/it/shared/RemovedResource.class
+quarkus.class-loading.removed-resources."io.quarkus\:quarkus-integration-test-main"=io/quarkus/it/rest/RemovedJaxRsApplication.class