HMS REGENT (Lt W N R Knox, DSC) sailed on 11 April 1943 from Malta to patrol in an area off the South coast of Italy. A submarine thought to be REGENT was sighted off Calabria on 13, 15 and 16 April. On 18 April she fired a torpedo at a merchant ship off the port of Monopoli but missed astern and the torpedo exploded on the shore. Later that day, a large explosion at sea was heard in Monopoli which is thought to have been REGENT striking a mine. She was listed as lost on 1 May 1943 when she failed to arrive at Port Said as expected.

The entire crew of sixty-three officers and ratings was lost. The first of four bodies (none were identified) was washed up near Brindisi on 1 May 1943. This was the body of an ERA dressed in overalls and wearing a DSEA escape kit. Another body was washed up at Santa Andrea di Missipezza on 15 May 1943 also wearing a DSEA kit. On 16 May a body (of either an Officer or a Petty Officer) was washed up at Torre Santo Stefano, north of Otranto and, on the same day, another body was washed up at Castro Marina. The bodies were later buried at the Bari war graves cemetery. Two of the head stones say HMS REGENT but have the incorrect date of the 16 April 1943.

In May 2022, a team led by Dr. Fabio Giuseppe Bisciotti discovered a wreck off Villanova, 19nm South East of Monopoli which they believed could be that of HMS REGENT. It is hoped that a more definitive identification will be made in the near future. The Royal Navy has said they could not yet confirm the discovery, due to the wreck being upside down and the fact that key sections buried in the seabed, however, they may confirm the wreck as being that of HMS REGENT as further information comes to light.