Forestieri was substituted at half-time in Monday’s Steel City derby with the recurrence of a hamstring injury, while Portugal international Joao is sidelined with a knee problem.
Both will definitely miss tomorrow’s Championship trip to Derby County, but with 11 matches remaining this season, Bruce knows games are quickly running out.
"It is a frustration absolutely but it is more frustrating for a player,” said Bruce. “The one thing you don't want to be as a football player is injured.
"It is the bane of your life and mentally you have to deal with it in your own way.
"As I have said, the club have had its fair share of long-term injuries which is a concern and a worry.
"However, it is what it is so I have got to try and fix it if I possibly can.
"He (Forestieri) had a scan yesterday. Unfortunately, he has a slight hamstring strain.
"We are trying to find out whether it is related to his old injury.
“We don't think so but obviously it is a concern because it keeps happening which is not great.”
Asked if he knew how long Forestieri - who has seen his season disrupted by injuries and suspensions - could be out for, Bruce replied: "Unfortunately no. We have to see and get the scans read properly.
"If it was anybody else with a normal hamstring that he has got, you would maybe say two to three weeks but with Fernando it is unfortunately an ongoing problem which we have to deal with.”
Bruce’s prognosis on Joao - who has netted nine goals for the Owls this season - was also bleak.
"He has a knee injury,” said Bruce. "That's another one. How long is a piece of string.”
Bruce has promised an investigation as to why the Owls have been plagued with long-term injuries over the last two years.
At one stage last season, Wednesday were missing 16 first-teamers, and it has been in double figures this campaign too.
"We have had our fair share of injuries which some are still trying to clear up,” said Bruce, who only arrived at Hillsborough five weeks ago. “It has to be said the club have been dogged with injuries for the past 18 months to two years.
"It is something we will look and try and address and see if we can find out what is the cause.
“One is bad enough but the club have had four or five which is unhealthy to say the least, especially to your top players as well. It is cruel.”
Hooper - who has not played since Boxing Day 2017 - was due to return for the Owls’ Under-23s today, following groin surgery.
While Winnall - the 28-year-old has made four substitute appearances this term after 10 months out with a knee injury - could be included in the squad for tomorrow’s trip to Derby.