Pizarro, Frings and Fritz missing for Bremen
"These injuries are hitting us hard," coach Thomas Schaaf said on the club's website.
"We are losing a lot of quality ahead of the challenges we face."
Peruvian striker Pizarro and Fritz were ruled out with muscle injuries while Frings was left nursing a big bruise on his hip after their 3-2 win over rivals Hamburg SV on Saturday.
Pizarro had just come back after missing several weeks with a muscle injury.
"We hope the three of them can quickly come back but there is the danger of them missing the next two games," said Schaaf.
Werder were already without injured defenders Naldo, Petri Pasanen and Sebastian Boenisch for the Group A match in Italy.