diff --git a/tsdb/querier.go b/tsdb/querier.go
index 72b6b51414..4342d60985 100644
--- a/tsdb/querier.go
+++ b/tsdb/querier.go
@@ -21,6 +21,7 @@ import (
 
 	"github.com/oklog/ulid"
 	"github.com/pkg/errors"
+	"golang.org/x/exp/slices"
 
 	"github.com/prometheus/prometheus/model/histogram"
 	"github.com/prometheus/prometheus/model/labels"
@@ -244,6 +245,41 @@ func PostingsForMatchers(ix IndexReader, ms ...*labels.Matcher) (index.Postings,
 			labelMustBeSet[m.Name] = true
 		}
 	}
+	isSubtractingMatcher := func(m *labels.Matcher) bool {
+		if !labelMustBeSet[m.Name] {
+			return true
+		}
+		return (m.Type == labels.MatchNotEqual || m.Type == labels.MatchNotRegexp) && m.Matches("")
+	}
+	someSubtractingMatchers, someIntersectingMatchers := false, false
+	for _, m := range ms {
+		if isSubtractingMatcher(m) {
+			someSubtractingMatchers = true
+		} else {
+			someIntersectingMatchers = true
+		}
+	}
+
+	if someSubtractingMatchers && !someIntersectingMatchers {
+		// If there's nothing to subtract from, add in everything and remove the notIts later.
+		// We prefer to get AllPostings so that the base of subtraction (i.e. allPostings)
+		// doesn't include series that may be added to the index reader during this function call.
+		k, v := index.AllPostingsKey()
+		allPostings, err := ix.Postings(k, v)
+		if err != nil {
+			return nil, err
+		}
+		its = append(its, allPostings)
+	}
+
+	// Sort matchers to have the intersecting matchers first.
+	// This way the base for subtraction is smaller and
+	// there is no chance that the set we subtract from
+	// contains postings of series that didn't exist when
+	// we constructed the set we subtract by.
+	slices.SortStableFunc(ms, func(i, j *labels.Matcher) bool {
+		return !isSubtractingMatcher(i) && isSubtractingMatcher(j)
+	})
 
 	for _, m := range ms {
 		switch {
@@ -312,16 +348,6 @@ func PostingsForMatchers(ix IndexReader, ms ...*labels.Matcher) (index.Postings,
 		}
 	}
 
-	// If there's nothing to subtract from, add in everything and remove the notIts later.
-	if len(its) == 0 && len(notIts) != 0 {
-		k, v := index.AllPostingsKey()
-		allPostings, err := ix.Postings(k, v)
-		if err != nil {
-			return nil, err
-		}
-		its = append(its, allPostings)
-	}
-
 	it := index.Intersect(its...)
 
 	for _, n := range notIts {
diff --git a/tsdb/querier_test.go b/tsdb/querier_test.go
index e9dd3b75f4..8cfd5d1412 100644
--- a/tsdb/querier_test.go
+++ b/tsdb/querier_test.go
@@ -22,6 +22,7 @@ import (
 	"path/filepath"
 	"sort"
 	"strconv"
+	"sync"
 	"testing"
 	"time"
 
@@ -2194,6 +2195,71 @@ func TestPostingsForMatchers(t *testing.T) {
 	}
 }
 
+// TestQuerierIndexQueriesRace tests the index queries with racing appends.
+func TestQuerierIndexQueriesRace(t *testing.T) {
+	const testRepeats = 1000
+
+	testCases := []struct {
+		matchers []*labels.Matcher
+	}{
+		{
+			matchers: []*labels.Matcher{
+				// This matcher should involve the AllPostings posting list in calculating the posting lists.
+				labels.MustNewMatcher(labels.MatchNotEqual, labels.MetricName, "metric"),
+			},
+		},
+		{
+			matchers: []*labels.Matcher{
+				// The first matcher should be effectively the same as AllPostings, because all series have m=0
+				// If it is evaluated first, then __name__=metric will contain more series than m=0.
+				labels.MustNewMatcher(labels.MatchNotEqual, "m", "0"),
+				labels.MustNewMatcher(labels.MatchEqual, labels.MetricName, "metric"),
+			},
+		},
+	}
+
+	for _, c := range testCases {
+		c := c
+		t.Run(fmt.Sprintf("%v", c.matchers), func(t *testing.T) {
+			db := openTestDB(t, DefaultOptions(), nil)
+			h := db.Head()
+			t.Cleanup(func() {
+				require.NoError(t, db.Close())
+			})
+			ctx, cancel := context.WithCancel(context.Background())
+			wg := &sync.WaitGroup{}
+			wg.Add(1)
+			go appendSeries(t, ctx, wg, h)
+			t.Cleanup(wg.Wait)
+			t.Cleanup(cancel)
+
+			for i := 0; i < testRepeats; i++ {
+				q, err := db.Querier(ctx, math.MinInt64, math.MaxInt64)
+				require.NoError(t, err)
+
+				values, _, err := q.LabelValues("n", c.matchers...)
+				require.NoError(t, err)
+				require.Emptyf(t, values, `label values for label "n" should be empty`)
+			}
+		})
+	}
+}
+
+func appendSeries(t *testing.T, ctx context.Context, wg *sync.WaitGroup, h *Head) {
+	defer wg.Done()
+
+	for i := 0; ctx.Err() != nil; i++ {
+		app := h.Appender(context.Background())
+		_, err := app.Append(0, labels.FromStrings(labels.MetricName, "metric", "n", strconv.Itoa(i), "m", "0"), 0, 0)
+		require.NoError(t, err)
+		err = app.Commit()
+		require.NoError(t, err)
+
+		// Throttle down the appends to keep the test somewhat nimble.
+		time.Sleep(time.Millisecond)
+	}
+}
+
 // TestClose ensures that calling Close more than once doesn't block and doesn't panic.
 func TestClose(t *testing.T) {
 	dir := t.TempDir()