diff --git a/changelogs/head.asciidoc b/changelogs/head.asciidoc
index e556905885..f778ce733d 100644
--- a/changelogs/head.asciidoc
+++ b/changelogs/head.asciidoc
@@ -13,6 +13,7 @@ https://github.com/elastic/apm-server/compare/7.13\...master[View commits]
 * Fix panic due to misaligned 64-bit access on 32-bit architectures {pull}5277[5277]
 * Fixed tail-based sampling pubsub to use _seq_no correctly {pull}5126[5126]
 * Removed service name from dataset {pull}5451[5451]
+* Fix panic on Fleet policy change when transaction metrics or tail-based sampling are enabled {pull}5670[5670]
 
 [float]
 ==== Intake API Changes
diff --git a/x-pack/apm-server/main.go b/x-pack/apm-server/main.go
index 0cf2df7369..f50ef4e79a 100644
--- a/x-pack/apm-server/main.go
+++ b/x-pack/apm-server/main.go
@@ -65,6 +65,7 @@ func newProcessors(args beater.ServerParams) ([]namedProcessor, error) {
 			return nil, errors.Wrapf(err, "error creating %s", name)
 		}
 		processors = append(processors, namedProcessor{name: name, processor: agg})
+		aggregationMonitoringRegistry.Remove("txmetrics")
 		monitoring.NewFunc(aggregationMonitoringRegistry, "txmetrics", agg.CollectMonitoring, monitoring.Report)
 	}
 	if args.Config.Aggregation.ServiceDestinations.Enabled {
@@ -86,6 +87,7 @@ func newProcessors(args beater.ServerParams) ([]namedProcessor, error) {
 		if err != nil {
 			return nil, errors.Wrapf(err, "error creating %s", name)
 		}
+		samplingMonitoringRegistry.Remove("tail")
 		monitoring.NewFunc(samplingMonitoringRegistry, "tail", sampler.CollectMonitoring, monitoring.Report)
 		processors = append(processors, namedProcessor{name: name, processor: sampler})
 	}
@@ -232,16 +234,18 @@ func runServerWithProcessors(ctx context.Context, runServer beater.RunServerFunc
 	return g.Wait()
 }
 
-var rootCmd = cmd.NewXPackRootCommand(beater.NewCreator(beater.CreatorParams{
-	WrapRunServer: func(runServer beater.RunServerFunc) beater.RunServerFunc {
-		return func(ctx context.Context, args beater.ServerParams) error {
-			processors, err := newProcessors(args)
-			if err != nil {
-				return err
-			}
-			return runServerWithProcessors(ctx, runServer, args, processors...)
+func wrapRunServer(runServer beater.RunServerFunc) beater.RunServerFunc {
+	return func(ctx context.Context, args beater.ServerParams) error {
+		processors, err := newProcessors(args)
+		if err != nil {
+			return err
 		}
-	},
+		return runServerWithProcessors(ctx, runServer, args, processors...)
+	}
+}
+
+var rootCmd = cmd.NewXPackRootCommand(beater.NewCreator(beater.CreatorParams{
+	WrapRunServer: wrapRunServer,
 }))
 
 func main() {
diff --git a/x-pack/apm-server/main_test.go b/x-pack/apm-server/main_test.go
index 967130b069..261ece10ca 100644
--- a/x-pack/apm-server/main_test.go
+++ b/x-pack/apm-server/main_test.go
@@ -7,8 +7,23 @@ package main
 // This file is mandatory as otherwise the apm-server.test binary is not generated correctly.
 
 import (
+	"context"
 	"flag"
 	"testing"
+
+	"github.com/stretchr/testify/assert"
+	"github.com/stretchr/testify/require"
+
+	"github.com/pkg/errors"
+	"go.elastic.co/apm/apmtest"
+
+	"github.com/elastic/beats/v7/libbeat/logp"
+	"github.com/elastic/beats/v7/libbeat/monitoring"
+	"github.com/elastic/beats/v7/libbeat/paths"
+
+	"github.com/elastic/apm-server/beater"
+	"github.com/elastic/apm-server/beater/config"
+	"github.com/elastic/apm-server/model/modelprocessor"
 )
 
 var systemTest *bool
@@ -28,3 +43,42 @@ func TestSystem(t *testing.T) {
 		main()
 	}
 }
+
+func TestMonitoring(t *testing.T) {
+	// samplingMonitoringRegistry will be nil, as under normal circumstances
+	// we rely on apm-server/sampling to create the registry.
+	samplingMonitoringRegistry = monitoring.NewRegistry()
+
+	var aggregationMonitoringSnapshot, tailSamplingMonitoringSnapshot monitoring.FlatSnapshot
+	runServerError := errors.New("runServer")
+	runServer := func(ctx context.Context, args beater.ServerParams) error {
+		aggregationMonitoringSnapshot = monitoring.CollectFlatSnapshot(aggregationMonitoringRegistry, monitoring.Full, false)
+		tailSamplingMonitoringSnapshot = monitoring.CollectFlatSnapshot(samplingMonitoringRegistry, monitoring.Full, false)
+		return runServerError
+	}
+	runServer = wrapRunServer(runServer)
+
+	home := t.TempDir()
+	err := paths.InitPaths(&paths.Path{Home: home})
+	require.NoError(t, err)
+
+	cfg := config.DefaultConfig()
+	cfg.Aggregation.Transactions.Enabled = true
+	cfg.Sampling.Tail.Enabled = true
+	cfg.Sampling.Tail.Policies = []config.TailSamplingPolicy{{SampleRate: 0.1}}
+
+	// Call the wrapped runServer twice, to ensure metric registration does not panic.
+	for i := 0; i < 2; i++ {
+		err := runServer(context.Background(), beater.ServerParams{
+			Config:         cfg,
+			Logger:         logp.NewLogger(""),
+			Tracer:         apmtest.DiscardTracer,
+			BatchProcessor: modelprocessor.Nop{},
+			Managed:        true,
+			Namespace:      "default",
+		})
+		assert.Equal(t, runServerError, err)
+		assert.NotEqual(t, monitoring.MakeFlatSnapshot(), aggregationMonitoringSnapshot)
+		assert.NotEqual(t, monitoring.MakeFlatSnapshot(), tailSamplingMonitoringSnapshot)
+	}
+}