It will be only the second time since Raymond Domenech became coach in July 2004 that Les Bleus have to manage without both their best strikers.
"We have to do without our best two goals scorers," Domenech told reporters. "It seems obvious to me that it's going to more difficult to find the net."
Trezeguet has scored 31 goals in 59 internationals, one more than Henry, his former Monaco team mate, who has played 73 times for his country.
France need victory in Berne to book their place at next year's World Cup.
"The team doesn't look the same when they are not here," goalkeeper Gregory Coupet said. "It's a blow to have them both injured at the same time."
Henry was a key figure in the 1-0 victory over Ireland last month, slotting a brilliant winner in the middle of the second half.
Domenech is likely to turn to Djibril Cisse and Sylvain Wiltord up front.
Cisse scored twice to inspire France to a 3-0 victory over the Faroe Islands in September and Wiltord, a regular under Domenech, has scored 23 goals and 73 caps.
"We have played without Henry and Trezeguet," Domenech said. "We have versatile players in the squad and I'm not really concerned about them."
Domenech has also been boosted by the international return of Zinedine Zidane who has scored 27 international goals, although the Real Madrid playmaker has a groin problem and missed training on Tuesday and Wednesday.
More from rediff