Guardiola added Nathan Ake will be back in the squad but Oleksandr Zinchenko will remain absent after both players missed last week's win over Chelsea.
City, leading the league standings with 56 points, have not dropped a point since losing 2-0 to Crystal Palace back in October and will look for their 13th straight win when they travel to the south coast on Saturday.
Ralph Hasenhuettl's Southampton, who held City to a goalless draw earlier this season, have won only five times so far but Guardiola heaped praise on his counterpart and opponents ahead of the match.
"They have the best free-kick taker in the world," he said, referring to midfielder James Ward-Prowse. "As a set-piece taker, he is exceptional.
"The quality they have, the manager is exceptional, one of the best in the Premier League by far... It's always a tough game. Our players know we have an incredible challenge tomorrow."