In May 1942, McKean was sent to the South Pacific, where she arrived in time to take part in the invasion of Tulagi in early August. During the long and difficult campaign to hold Guadalcanal, she performed in logistics support and escort duties. After an overhaul in the first part of 1943, McKean returned to the South Pacific to join in the Allied offensive up the Solomon Islands chain. She participated in landings at Rendova and New Georgia in June and July 1943, and at Vella Lavella in August. During late October and early November, she landed troops at Mono Island, Choiseul and Cape Torokina on Bougainville.
During the morning darkness on 17 November 1943, while bringing up more Marines to Bougainville, McKean was torpedoed by a Japanese plane. She sank within a half hour with the loss of more than a hundred crewmen and Marines.
In addition to the Navy Unit Commendation, McKean earned four battle stars on her Asiatic-Pacific campaign ribbon.