The ship was badly damaged when she rammed the submarine and she was given temporary repairs at Gibraltar between 22 October and 20 November. She escorted a troop convoy from Gibraltar to Malta in late November during Operation Collar. Permanent repairs were made at Malta between 29 November and 20 February 1941. After her repairs were completed, "Hotspur" was assigned to the 2nd Destroyer Flotilla of the Mediterranean Fleet. The ship escorted the capital ships of the Mediterranean Fleet during the Battle of Cape Matapan in March 1941. In mid-April she escorted the fast transport and three battleships from Alexandria to Malta before going on to escort the battleships as they bombarded Tripoli on 20 April. After refuelling in Alexandria on 23 April, "Hotspur" sailed for Greece to begin evacuating British and Australian troops from the beaches. On 8 May, the ship again escorted the capital ships of the Mediterranean Fleet as they covered another convoy from Alexandria to Malta before being detached to escort the light cruiser as she bombarded Benghazi harbour on 7/8 May and sank two Italian merchant ships. During the evacuation of Crete "Hotspur" had to scuttle the destroyer on 29 May after the latter ship's steering had been disabled by a near miss by a bomb. The ship escorted the LSI(L) during the opening stage of the Syria-Lebanon Campaign of June 1941 and also hunted for French submarines. From July to November, "Hotspur" escorted convoys to Tobruk On 25 November, she was escorting the battleship when that ship was torpedoed by . "Hotspur" and the other escorting destroyers rescued 451 men. The ship escorted the light cruiser when she bombarded Derna in early December. While escorting a convoy, "Hotspur" and her sister, , sank on 23 December north of Sollum. During a convoy to Malta in January 1942, the ship was detailed to escort the merchant ship "Thermopylae" to Benghazi when she started having engine trouble. En route, however, "Thermopylae" was sunk by air attack on 19 January. On 23 March "Hotspur" was transferred to the Eastern Fleet in the Indian Ocean and was assigned to Force A of the fleet during the Indian Ocean raid by the Japanese in early April 1942. The ship returned to the Mediterranean to participate in Operation Vigorous, another convoy from Alexandria to Malta, in June. "Hotspur" was forced to sink her sister, "Hasty", after the latter was damaged by a torpedo from German motor torpedo boat "S-55".