Striker Karim Benzema (groin), winger Franck Ribery (calf), and right back Bacary Sagna (broken leg) have all been ruled out of playing against Albania.
Having spent more than a year rebuilding France following the 2010 World Cup debacle, Blanc suddenly has to reshuffle his team all over again, recalling fringe players like Djibril Cisse and Bafetimbi Gomis for Friday's match and for Tuesday's crucial clash against Bosnia-Herzegovina, which is only one point behind in Group D.
''Everything can be taken into consideration, but we need to keep our shape and balance,'' Blanc said. ''Keeping possession will be the key factor, our objective is to win both matches.''
France tops the group with 17 points, and if it beats Albania at Stade de France it will then need only need to draw against Bosnia to guarantee a place at Euro 2012.
In the unlikely event that Bosnia loses at home to Luxembourg on Friday, a win would be enough to qualify France.
Blanc has injury problems in attack and defense, with Barcelona leftback Eric Abidal rated as highly doubtful to play because of a tight hamstring. Striker Kevin Gameiro (knee), midfielder Blaise Matuidi (thigh) are both sidelined.
Fullbacks Mathieu Debuchy and Jeremy Mathieu have been called up as cover in defense and could make their international debuts.
Losing Benzema and Ribery is a big blow to Blanc. Both made excellent starts to their domestic seasons with Real Madrid and Bayern Munich respectively, and Blanc admits he will miss their creative drive.
Benzema, in particular, has become a crucial player since Blanc took over the France team, scoring crucial goals in Euro 2012 qualifiers away to Albania, Bosnia, at home to Luxembourg, and in friendlies against England and Brazil.
''Karim is an important player for us. He's our No. 1,'' Blanc said. ''I would have liked to have him available.''
The injuries to Benzema and Gameiro, however, have opened the door for strikers Cisse and Gomis to salvage their international careers.
The 30-year-old Cisse has not played for France since the 2-1 defeat by South Africa at the World Cup in June last year, while Gomis' last appearance came two years ago.
With Benzema scoring regularly, and Marseille's Loic Remy jostling with Gameiro to be Blanc's backup striker, there appeared little chance either would return for France any time soon, or until the injuries disrupted Blanc's plans.
Now they have a chance to stake their claim by scoring the goals to take France to Euro 2012.
''If I've been called up, it's that I can help the team,'' said the much-traveled Cisse, who now plays for Lazio and has scored nine goals in 40 matches for France. ''If I can take someone's place, then I will. I'm a competitor.''
When Gomis scored twice on his international debut to edge out Cisse for a place in France's Euro 2008 squad, his international future looked bright. But the goals dried up at club level with Lyon, until he was paired with Argentina striker Lisandro Lopez to form one of the most dangerous partnerships in the French first division.
''Benzema's been in great form this season, but I don't feel under any particular pressure,'' Gomis said. ''I am ready, and if I was called up it means I have the qualities to play.''
Albania has won only two of its eight qualifiers, at home against Luxembourg and Belarus, and appears to pose little attacking threat.
But with France needing a win to boost its confidence ahead of Bosnia's visit, France's defenders must be wary of conceding the kind of sloppy goal it did late on when it opened its qualifying campaign with a 1-0 home defeat to Belarus.
''Albania will come here to try and get a result,'' Gomis said. ''I expect them to defend in numbers and try and look for a chance.''