The boat was ordered to operate against enemy aircraft carriers that entered the Western Mediterranean from Gibraltar to launch fighter aircraft for Malta.

In the afternoon on 1 May, U-573 was badly damaged during an air attack and called for help. U-74 left its operational area to assist and was en route unsuccessfully attacked by HMS Unbroken at 22.22 hours. No contact was made with the U-boat in distress during the night, which reached the port of Cartagena in neutral Spain under own power the next morning. However, a Catalina flying boat still searching for the crippled U-boat located U-375 during the afternoon on 2 May and its sighting report brought two British destroyers to the scene, which searched the area and located and sank the nearby U-74 while U-375 escaped.