Devon Smith called up to replace Gayle
Smith, 33, has represented the West Indies in 33 Tests since making his debut in 2003 against Australia in Guyana.
The pugnacious left handed opener — who scored a century in his latest first class match — has scored one Test century and five half centuries and averages a shade under 37 in First Class cricket.
Gayle is the second experienced player the squad has seen drop out as Dwayne Bravo pulled out last month citing personal reasons.
The series against South Africa will be the first for the West Indies since they quit India four matches into a five-game, one-day series in October after a pay dispute between players and the board, with a Twenty20 international and three Tests to play.
The West Indies Cricket Board has since set up a task force to explore the controversy with a report due on December 18.
West Indies will play three Tests, three Twenty20 internationals and five one-dayers in South Africa.
Denesh Ramdin (Capt), Sulieman Benn, Jermaine Blackwood, Kraigg Braithwaite, Shivnarine Chanderpaul, Sheldon Cottrell, Assad Fudadin, Shannon Gabriel, Jason Holder, Leon Johnson, Kemar Roach, Marlon Samuels, Devon Smith, Jerome Taylor, Chadwick Walton