Bruce has likened the Ghana international to former Manchester United and Aston Villa centre-back Paul McGrath, who infamously struggled to train between matches because of long-standing knee problems.
Whenever Mensah has played for Sunderland this season he has regularly looked one of the best players on the pitch, with his manager claiming he is rightly regarded as one of the best in Europe.
But because of chronic problems with his spine, Mensah finds it difficult to play every week and, ultimately, that has contributed to the hamstring injury threatening to keep him out of tomorrow's trip to Anfield.
Lyon paid £8.4m for him just 18 months ago and are keen to recoup a sizeable chunk of that fee if they are to allow Sunderland to make the loan arrangement permanent in the summer.
While Bruce is unwilling to go anywhere near that sum, he also appreciates that replacing Mensah in his squad for next season would be extremely tough.
We will try to do something but because of his injuries it's very difficult. He is an exceptionally gifted player but we will have to sit down and talk with Lyon, where he has three years left, said Bruce.
It's a gamble. Paul McGrath went to Villa from Man United for £400,000 and he won their player of the year four years in a row and we know all about his problems.
I went to Man United (as a player) and I was thinking how am I going to replace him He's magnificent.' Paul was unbelievable and Mensah comes into that category.
He's naturally a magnificent footballer. If you see him stripped it's amazing that he has this unbelievable body which falls to bits.
It's just a crying shame he has these problems. If you have one of those players then you need a more than capable deputy.
With Mensah unlikely to figure at Liverpool, Bruce must decide whether to slot Anton Ferdinand back into the middle after performing well at left-back or hand January buy Matthew Kilgallon another chance.