The Spanish star looks set to be out for the games with Chelsea, Wigan and a return to his former club Atletico Madrid in the Champions League while Babel damaged his ankle playing for Holland in their 1-0 win in Norway and he too is a doubt for the weekend.
Babel, who missed Euro 2008 with ankle ligament problems, played no further part in Wednesday's match after going down in a tackle from Morten Gamst Pedersen on 26 minutes.
"I am very disappointed about this because it now looks like we will lose Fernando for three very important games," Benitez told the club's official website.
"We have Wigan at home and Chelsea away in the league and Atletico Madrid away in the Champions League, so to lose any players is a big blow.
"The initial reports say Fernando is likely to be out for around ten days and that would mean he would miss these three games.
"There are too many international games and the demands on the players are too much," Benitez added. "Someone needs to analyse this situation because it is putting the players at risk of injury."
He added: "Maybe the answer is for there to be a two-tier qualifying system because there are too many games in the qualifiers for the World Cup and the European Championships which are not competitive but which still place great demands on the players.
"These fixtures are unnecessary and maybe it would be better if the weaker countries played one another and the best of them went to play the stronger countries in the qualifiers."