German submarine U-378 was a Type VIIC U-boat of Nazi Germany's Kriegsmarine during World War II. She carried out eight patrols before being sunk by US aircraft on 20 October 1943 in mid-Atlantic at position 47°40′N 28°27′W / 47.667°N 28.450°W. She was a member of 16 wolfpacks. She sank one warship.