The 30-year-old limped out of Sunday's 1-1 draw with Arminia Bielefeld in Germany and sat out the 3-1 defeat by Hannover 96 on Wednesday night.
O'Shea will also miss Saturday's clash with Borussia Monchengladbach and faces a further fortnight on the sidelines as he attempts to return to fitness, but his manager will not rush him.
Bruce told the Sunderland Echo: "It's disappointing that John hasn't played here, but we have still got three weeks left.
"We need him to be ready in a few weeks' time, not now. We have got games when we get back.
"It would be nice to see him play, but he got his leg in a difficult position against Arminia Bielefeld on Sunday and strained a muscle.
"We will have to keep an eye on how he is. The last thing we want to do now is risk anybody. If they have got anything slight, I would rather them give training and the games a rest.
"But the vast majority got through the game yesterday and hopefully everyone's okay."