diff --git a/src/net_processing.cpp b/src/net_processing.cpp
index e1674b6d514..336669a8545 100644
--- a/src/net_processing.cpp
+++ b/src/net_processing.cpp
@@ -3329,6 +3329,16 @@ void PeerManagerImpl::ProcessCompactBlockTxns(CNode& pfrom, Peer& peer, const Bl
 
         PartiallyDownloadedBlock& partialBlock = *range_flight.first->second.second->partialBlock;
 
+        if (partialBlock.header.IsNull()) {
+            // It is possible for the header to be empty if a previous call to FillBlock wiped the header, but left
+            // the PartiallyDownloadedBlock pointer around (i.e. did not call RemoveBlockRequest). In this case, we
+            // should not call LookupBlockIndex below.
+            RemoveBlockRequest(block_transactions.blockhash, pfrom.GetId());
+            Misbehaving(peer, "previous compact block reconstruction attempt failed");
+            LogDebug(BCLog::NET, "Peer %d sent compact block transactions multiple times", pfrom.GetId());
+            return;
+        }
+
         // We should not have gotten this far in compact block processing unless it's attached to a known header
         const CBlockIndex* prev_block{Assume(m_chainman.m_blockman.LookupBlockIndex(partialBlock.header.hashPrevBlock))};
         ReadStatus status = partialBlock.FillBlock(*pblock, block_transactions.txn,
@@ -3340,6 +3350,9 @@ void PeerManagerImpl::ProcessCompactBlockTxns(CNode& pfrom, Peer& peer, const Bl
         } else if (status == READ_STATUS_FAILED) {
             if (first_in_flight) {
                 // Might have collided, fall back to getdata now :(
+                // We keep the failed partialBlock to disallow processing another compact block announcement from the same
+                // peer for the same block. We let the full block download below continue under the same m_downloading_since
+                // timer.
                 std::vector<CInv> invs;
                 invs.emplace_back(MSG_BLOCK | GetFetchFlags(peer), block_transactions.blockhash);
                 MakeAndPushMessage(pfrom, NetMsgType::GETDATA, invs);
diff --git a/test/functional/p2p_compactblocks.py b/test/functional/p2p_compactblocks.py
index 56186bc1eb4..a2a3ffe2d82 100755
--- a/test/functional/p2p_compactblocks.py
+++ b/test/functional/p2p_compactblocks.py
@@ -558,6 +558,42 @@ class CompactBlocksTest(BitcoinTestFramework):
         test_node.send_and_ping(msg_block(block))
         assert_equal(node.getbestblockhash(), block.hash_hex)
 
+    # Multiple blocktxn responses will cause a node to get disconnected.
+    def test_multiple_blocktxn_response(self, test_node):
+        node = self.nodes[0]
+        utxo = self.utxos[0]
+
+        block = self.build_block_with_transactions(node, utxo, 2)
+
+        # Send compact block
+        comp_block = HeaderAndShortIDs()
+        comp_block.initialize_from_block(block, prefill_list=[0], use_witness=True)
+        test_node.send_and_ping(msg_cmpctblock(comp_block.to_p2p()))
+        absolute_indexes = []
+        with p2p_lock:
+            assert "getblocktxn" in test_node.last_message
+            absolute_indexes = test_node.last_message["getblocktxn"].block_txn_request.to_absolute()
+        assert_equal(absolute_indexes, [1, 2])
+
+        # Send a blocktxn that does not succeed in reconstruction, triggering
+        # getdata fallback.
+        msg = msg_blocktxn()
+        msg.block_transactions = BlockTransactions(block.hash_int, [block.vtx[2]] + [block.vtx[1]])
+        test_node.send_and_ping(msg)
+
+        # Tip should not have updated
+        assert_equal(int(node.getbestblockhash(), 16), block.hashPrevBlock)
+
+        # We should receive a getdata request
+        test_node.wait_for_getdata([block.hash_int], timeout=10)
+        assert test_node.last_message["getdata"].inv[0].type == MSG_BLOCK or \
+               test_node.last_message["getdata"].inv[0].type == MSG_BLOCK | MSG_WITNESS_FLAG
+
+        # Send the same blocktxn and assert the sender gets disconnected.
+        with node.assert_debug_log(['previous compact block reconstruction attempt failed']):
+            test_node.send_without_ping(msg)
+        test_node.wait_for_disconnect()
+
     def test_getblocktxn_handler(self, test_node):
         node = self.nodes[0]
         # bitcoind will not send blocktxn responses for blocks whose height is
@@ -977,6 +1013,12 @@ class CompactBlocksTest(BitcoinTestFramework):
         # The previous test will lead to a disconnection. Reconnect before continuing.
         self.segwit_node = self.nodes[0].add_p2p_connection(TestP2PConn())
 
+        self.log.info("Testing handling of multiple blocktxn responses...")
+        self.test_multiple_blocktxn_response(self.segwit_node)
+
+        # The previous test will lead to a disconnection. Reconnect before continuing.
+        self.segwit_node = self.nodes[0].add_p2p_connection(TestP2PConn())
+
         self.log.info("Testing invalid index in cmpctblock message...")
         self.test_invalid_cmpctblock_message()