Fletcher was ruled out of the final eight games of the campaign after damaging ankle ligaments on international duty with Scotland in March, while the red card Sessegnon picked up at Aston Villa on Monday evening means he will sit out the clashes with Stoke, Southampton and Tottenham as the Black Cats look to end their relegation fears.
Between them, the pair have scored 18 Premier League goals this season, a little short of half the 39 the team has managed in total, and with January signing Danny Graham still to open his account, there is a genuine concern over how they are going to get themselves out of trouble.
However, Di Canio is convinced there is still strike-power within his squad as he prepares for Monday night's home clash with Stoke.
He said: "I don't talk about Stephane because he is out, I will focus my attention on my [remaining] players.
"We have enough quality to score goals to win games, especially because we play at home, which is really important.
"It means 39,000, 40,000 people are pushing for the players, which gives them extra adrenaline and motivation to give their best.
"We have quality. Danny Graham hasn't scored yet, but now I am sure the time has come when he will score because in the next few games, he will be crucial.
"We have Adam Johnson who is able of scoring. We have different ways to damage the opponent, so I am not worried, to be honest.
"I am not the kind of manager who cries - obviously I would like to have all my players available and many options.
"But it's not possible and we are going to find a way to damage the opponent.
"I won't tell you now if we are going to change formation, if we change the system, but we are going to put on the field the best team we can to win the game and get three points."
Such is Sunderland's lack of specialist strikers - 20-year-old Connor Wickham is currently sidelined by a calf injury - that they launched an appeal against Sessegnon's dismissal for a challenge on Villa's Yacouba Sylla, although one which always looked doomed.
It was rejected by an independent regulatory commission, much to Di Canio's chagrin, and he has spent the days since working on a plan to plug the yawning gap in his attacking resources.
Sunderland will start the weekend five points clear of the relegation zone despite Monday's 6-1 drubbing at Villa Park, but know their situation could have worsened by the time they kick off against the Potters at the Stadium of Light.
It will be their second successive Monday night fixture, but Di Canio believes that can only be an advantage at this stage of the season.
He said: "It's an advantage, not a disadvantage, because if we are talking about what is going on on Saturday, if Wigan win, if Villa win, if Newcastle win, we have to win anyway; if they lose, we have to win anyway.
"Just because we fell in a trap the week before, I don't think we are so stupid.
"Whatever happens to the others, we are not going to underestimate this game because this slap was too much.
"Now we have a big, big scar showing on our body which reminds us if we play like that, we can have another one.
"We are not masochistic people, so I am sure we are going to perform properly.
"It doesn't mean that we are going to win 3-0, it means we are going to perform in terms of commitment, desire, concentration, dedication like we did against Everton and Newcastle. That's for sure."
Meanwhile, Sunderland confirmed on Friday that chief scout Bryan "Pop" Robson is to leave the club with immediate effect.