Fulham’s new signing misses the Group H tie at the Nelson Mandela Bay stadium with a right ankle injury picked up in Switzerland’s shock opening 1-0 defeat of World Cup favourites Spain.
The Swiss are hoping to have Senderos back should they seal their passage to the last 16.
A second round ticket is well within their grasp after they toppled European champions Spain in Durban on Wednesday.
Midfielder Gelson Fernandes’s second half goal gave Ottmar Hitzfeld’s men a maiden win over the Spanish in 85 years.
Hitzfeld underlined the importance of Senderos though to his side when he said: “It will be very difficult to replace him.”
Swiss striker and captain Alexander Frei and midfielder Valon Behrami, who both missed the opener with injury, are once again rated doubtful for Monday’s second World Cup outing.
Chile created their own bit of history when a first half strike from Jean Beausejour gave them a 1-0 win over Honduras to end a 13-game winless run spanning four World Cups.
The South Americans’ last success in the tournament came in 1962 when they beat the then Yugoslavia to finish third as hosts.
They faced Honduras without top striker Humberto Suazo, the leading scorer in the South American qualifiers with 10 goals who has been recovering from a leg injury.
Suazo completed a full training session on Friday and is set to make his 2010 World Cup debut against the Swiss.
Suazo was sorely missed and coach Marcelo Bielsa, who is desperate to reach the second round having failed to do so in 2002 with his native Argentina, expressed concern at the 1-0 scoreline.
“If the group is decided on goal difference then we will rue the chances we missed. We could have scored more goals and we were on top.”
The 54-year-old added: “We’ll try to win the next game because the objective is to pass to the next round and start writing new records.”
Hitzfeld for his part, speaking after the Spanish KO, described Switzerland’s win as “a gift”.
“It’s great to start the tournament with three unexpected points against one of the biggest contenders for the title.
“It’s an excellent start and exactly what we needed. We’ll now go into the Chile match with resolve and a great deal of self-confidence which we need to tackle the more difficult challenges ahead.”
After Monday’s clash Chile face Spain in Pretoria on Friday with Switzerland completing their first round against Honduras in Bloemfontein the same day.