"Spence" was attached to Destroyer Division (DesDiv) 46 of Destroyer Squadron (DesRon) 23. The squadron sailed on 22 September for Tulagi, Solomon Islands. On the 28th, she set a surface craft on fire with her main batteries near Kolombangara and then patrolled between that island and Vella Lavella. On the night of 1 and 2 October, Spence was with a force off Vella Lavella to interdict Japanese shipping and helped to destroy 20 Japanese barges. The DD then made two escort runs from Tulagi to Purvis Bay during the first part of the month and ended October supporting landings on the Treasury Islands.