Valon Behrami will miss Switzerland's 2010 FIFA World Cup Group H opener against Spain on Wednesday, coach Ottmar Hitzfeld has confirmed.
The Swiss will be without the West Ham United midfielder after he failed to recover from a thigh muscle injury suffered in a 1-1 warm-up draw with Italy in Geneva on 5 June.
Hitzfeld announced that he would also be without striker Alex Frei, the country's all-time leading scorer with 40 international goals, who has an ankle problem.
The loss of two senior players will be a massive blow for Switzerland, who already face a stern test against the reigning European champions and World Cup favourites in Durban.
"I have taken the decision. Alex Frei and Valon Behrami will not play against Spain," said Hitzfeld on Monday.
The German-born coach added that he hopes to have the pair available for Switzerland's second group-stage fixture against Chile in Nelson Mandela Bay/Port Elizabeth on Monday 21 June.
"It is better to spare them so we have both of them available against Chile," said Hitzfeld.
Behrami is set to be replaced by former Manchester City player Gelson Fernandes or UC Sampdoria midfielder Marco Padalino, who he played alongside at Swiss club FC Lugano as a teenager during the 2002/03 season.
Switzerland held an open training session at their Vanderbijlpark base on Monday, inviting local fans to bring their vuvuzela horns along in order to create an atmosphere similar to the one they will experience at the Moses Mabhida Stadium.
Hitzfeld and his squad will travel to Durban on Monday afternoon before holding a final training session at the newly-built 62,760-capacity stadium on Tuesday evening.
The Swiss have never beaten Spain in 18 previous meetings, losing 2-1 at Hillsborough during the 1966 World Cup and 3-0 in Washington DC at the 1994 finals.