diff --git a/.unreleased/PR_6209 b/.unreleased/PR_6209
new file mode 100644
index 00000000000..d31ead1c4de
--- /dev/null
+++ b/.unreleased/PR_6209
@@ -0,0 +1 @@
+Fixes: #6209 Allow enabling compression on hypertable with unique expression index
diff --git a/tsl/src/compression/create.c b/tsl/src/compression/create.c
index 0e741516151..ad1f59c2cce 100644
--- a/tsl/src/compression/create.c
+++ b/tsl/src/compression/create.c
@@ -956,6 +956,8 @@ validate_existing_indexes(Hypertable *ht, CompressColInfo *colinfo, Bitmapset *i
 		for (int i = 0; i < index->indnkeyatts; i++)
 		{
 			int attno = index->indkey.values[i];
+			if (attno == 0)
+				continue; /* skip check for expression column */
 			Form_hypertable_compression col_def = get_col_info_for_attnum(ht, colinfo, attno);
 			Ensure(col_def, "missing column definition for unique index");
 			if (col_def->segmentby_column_index < 1 && col_def->orderby_column_index < 1)
diff --git a/tsl/test/expected/compression_ddl.out b/tsl/test/expected/compression_ddl.out
index ac9a0d6041e..21254de876c 100644
--- a/tsl/test/expected/compression_ddl.out
+++ b/tsl/test/expected/compression_ddl.out
@@ -2392,3 +2392,20 @@ EXPLAIN (COSTS OFF) SELECT * FROM space_part ORDER BY time;
                      ->  Seq Scan on _hyper_36_135_chunk
 (35 rows)
 
+-- test creation of unique expression index does not interfere with enabling compression
+-- github issue 6205
+create table mytab (col1 varchar(100) not null, col2 integer not null,
+value double precision not null default 0, arrival_ts timestamptz not null, departure_ts timestamptz not null
+default current_timestamp);
+select create_hypertable('mytab', 'departure_ts');
+WARNING:  column type "character varying" used for "col1" does not follow best practices
+  create_hypertable  
+---------------------
+ (38,public,mytab,t)
+(1 row)
+
+create unique index myidx_unique ON
+mytab (lower(col1::text), col2, departure_ts, arrival_ts);
+alter table mytab set (timescaledb.compress);
+WARNING:  column "col2" should be used for segmenting or ordering
+WARNING:  column "arrival_ts" should be used for segmenting or ordering
diff --git a/tsl/test/sql/compression_ddl.sql b/tsl/test/sql/compression_ddl.sql
index 789b0a4aa07..e0ed32583a8 100644
--- a/tsl/test/sql/compression_ddl.sql
+++ b/tsl/test/sql/compression_ddl.sql
@@ -965,3 +965,14 @@ EXPLAIN (COSTS OFF) SELECT * FROM space_part ORDER BY time;
 INSERT INTO space_part VALUES
 ('2022-01-01 00:02', 1, 1, 1);
 EXPLAIN (COSTS OFF) SELECT * FROM space_part ORDER BY time;
+
+-- test creation of unique expression index does not interfere with enabling compression
+-- github issue 6205
+create table mytab (col1 varchar(100) not null, col2 integer not null,
+value double precision not null default 0, arrival_ts timestamptz not null, departure_ts timestamptz not null
+default current_timestamp);
+
+select create_hypertable('mytab', 'departure_ts');
+create unique index myidx_unique ON
+mytab (lower(col1::text), col2, departure_ts, arrival_ts);
+alter table mytab set (timescaledb.compress);