Alderweireld, 27, has missed Tottenham's last eight games due to a knee injury suffered in the 1-1 draw with West Brom in mid-October. While the Belgium international could be back in contention for the visit of Swansea City on 3 December, the trip across the capital to Stamford Bridge will come too soon for him.
"Danny Rose is suspended, Erik Lamela, Ben Davies and Toby Alderweireld are still out for Saturday," Pochettino told a press conference on Thursday (24 November).
Pochettino also faces a potential selection headache at left-back with Danny Rose suspended. The England international picked up his fifth booking of the season in the 3-2 victory over West Ham United and, with Ben Davies still recovering from an ankle injury, the Spurs coach is short of options.
Jan Vertonghen, who has regularly played at left-back for Belgium over the years, could be moved across to fill in against Chelsea.
"We have different options," Pochettino continued. "If you remember against Sunderland it was Jan who played left-back when Danny Rose was injured and Ben was a little tired (he'd played twice that week after playing twice for Wales).
"We can play Jan, we can play Kevin Wimmer, maybe we'll use Kieran Trippier on the left. We'll see. We have two training sessions ahead to decide what is best for the team."
While they are unbeaten in the league this season, Tottenham have won just one game from their last eight in all competitions, with Erik Lamela's absence seemingly contributing to that poor run of form. The Argentina international is also not available for the Chelsea match due to his ongoing hip injury.