diff --git a/CHANGELOG.md b/CHANGELOG.md
index eb99c02532..5edf441d56 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -19,6 +19,7 @@ We use *breaking* word for marking changes that are not backward compatible (rel
 ### Added
 
 ### Changed
+- [#2450](https://github.com/thanos-io/thanos/pull/2450) Store: regex-set optimization for `label=~"a|b|c"` matchers.
 
 ## [v0.12.0](https://github.com/thanos-io/thanos/releases/tag/v0.12.0) - 2020.04.15
 
diff --git a/pkg/store/bucket.go b/pkg/store/bucket.go
index e0a1084312..c7d81098a7 100644
--- a/pkg/store/bucket.go
+++ b/pkg/store/bucket.go
@@ -1502,6 +1502,15 @@ func toPostingGroup(lvalsFn func(name string) ([]string, error), m *labels.Match
 		return emptyPostingsGroup, nil
 	}
 
+	if m.Type == labels.MatchRegexp && len(findSetMatches(m.Value)) > 0 {
+		vals := findSetMatches(m.Value)
+		toAdd := make([]labels.Label, 0, len(vals))
+		for _, val := range vals {
+			toAdd = append(toAdd, labels.Label{Name: m.Name, Value: val})
+		}
+		return newPostingGroup(false, toAdd, nil), nil
+	}
+
 	// If the matcher selects an empty value, it selects all the series which don't
 	// have the label name set too. See: https://github.com/prometheus/prometheus/issues/3575
 	// and https://github.com/prometheus/prometheus/pull/3578#issuecomment-351653555.
diff --git a/pkg/store/bucket_test.go b/pkg/store/bucket_test.go
index 331660db80..0e5ccd7d64 100644
--- a/pkg/store/bucket_test.go
+++ b/pkg/store/bucket_test.go
@@ -1005,6 +1005,7 @@ func benchmarkExpandedPostings(
 	iNotEmpty := labels.MustNewMatcher(labels.MatchNotEqual, "i", "")
 	iNot2 := labels.MustNewMatcher(labels.MatchNotEqual, "n", "2"+postingsBenchSuffix)
 	iNot2Star := labels.MustNewMatcher(labels.MatchNotRegexp, "i", "^2.*$")
+	iRegexSet := labels.MustNewMatcher(labels.MatchRegexp, "i", "0"+postingsBenchSuffix+"|1"+postingsBenchSuffix+"|2"+postingsBenchSuffix)
 
 	series = series / 5
 	cases := []struct {
@@ -1029,6 +1030,7 @@ func benchmarkExpandedPostings(
 		{`n="1",i=~"1.+",j="foo"`, []*labels.Matcher{n1, i1Plus, jFoo}, int(float64(series) * 0.011111)},
 		{`n="1",i=~".+",i!="2",j="foo"`, []*labels.Matcher{n1, iPlus, iNot2, jFoo}, int(float64(series) * 0.1)},
 		{`n="1",i=~".+",i!~"2.*",j="foo"`, []*labels.Matcher{n1, iPlus, iNot2Star, jFoo}, int(1 + float64(series)*0.088888)},
+		{`i=~"0|1|2"`, []*labels.Matcher{iRegexSet}, 150}, // 50 series for "1", 50 for "2" and 50 for "3".
 	}
 
 	for _, c := range cases {
diff --git a/pkg/store/opts.go b/pkg/store/opts.go
new file mode 100644
index 0000000000..e95a623a70
--- /dev/null
+++ b/pkg/store/opts.go
@@ -0,0 +1,63 @@
+// Copyright (c) The Thanos Authors.
+// Licensed under the Apache License 2.0.
+
+package store
+
+import (
+	"strings"
+	"unicode/utf8"
+)
+
+// Bitmap used by func isRegexMetaCharacter to check whether a character needs to be escaped.
+var regexMetaCharacterBytes [16]byte
+
+// isRegexMetaCharacter reports whether byte b needs to be escaped.
+func isRegexMetaCharacter(b byte) bool {
+	return b < utf8.RuneSelf && regexMetaCharacterBytes[b%16]&(1<<(b/16)) != 0
+}
+
+func init() {
+	for _, b := range []byte(`.+*?()|[]{}^$`) {
+		regexMetaCharacterBytes[b%16] |= 1 << (b / 16)
+	}
+}
+
+// Copied from Prometheus querier.go, removed check for Prometheus wrapper.
+// Returns list of values that can regex matches.
+func findSetMatches(pattern string) []string {
+	escaped := false
+	sets := []*strings.Builder{{}}
+	for i := 0; i < len(pattern); i++ {
+		if escaped {
+			switch {
+			case isRegexMetaCharacter(pattern[i]):
+				sets[len(sets)-1].WriteByte(pattern[i])
+			case pattern[i] == '\\':
+				sets[len(sets)-1].WriteByte('\\')
+			default:
+				return nil
+			}
+			escaped = false
+		} else {
+			switch {
+			case isRegexMetaCharacter(pattern[i]):
+				if pattern[i] == '|' {
+					sets = append(sets, &strings.Builder{})
+				} else {
+					return nil
+				}
+			case pattern[i] == '\\':
+				escaped = true
+			default:
+				sets[len(sets)-1].WriteByte(pattern[i])
+			}
+		}
+	}
+	matches := make([]string, 0, len(sets))
+	for _, s := range sets {
+		if s.Len() > 0 {
+			matches = append(matches, s.String())
+		}
+	}
+	return matches
+}
diff --git a/pkg/store/opts_test.go b/pkg/store/opts_test.go
new file mode 100644
index 0000000000..e79fdf35bc
--- /dev/null
+++ b/pkg/store/opts_test.go
@@ -0,0 +1,53 @@
+// Copyright (c) The Thanos Authors.
+// Licensed under the Apache License 2.0.
+
+package store
+
+import (
+	"testing"
+
+	"github.com/thanos-io/thanos/pkg/testutil"
+)
+
+// Refer to https://github.com/prometheus/prometheus/issues/2651.
+func TestFindSetMatches(t *testing.T) {
+	cases := []struct {
+		pattern string
+		exp     []string
+	}{
+		// Simple sets.
+		{
+			pattern: "foo|bar|baz",
+			exp: []string{
+				"foo",
+				"bar",
+				"baz",
+			},
+		},
+		// Simple sets containing escaped characters.
+		{
+			pattern: "fo\\.o|bar\\?|\\^baz",
+			exp: []string{
+				"fo.o",
+				"bar?",
+				"^baz",
+			},
+		},
+		// Simple sets containing special characters without escaping.
+		{
+			pattern: "fo.o|bar?|^baz",
+			exp:     nil,
+		},
+		{
+			pattern: "foo\\|bar\\|baz",
+			exp: []string{
+				"foo|bar|baz",
+			},
+		},
+	}
+
+	for _, c := range cases {
+		matches := findSetMatches(c.pattern)
+		testutil.Equals(t, c.exp, matches)
+	}
+}