They would miss Pavelski and Hertl more than Karlsson. Karlsson hasn't been 100% the whole playoffs and as a result has mostly been a defensive liability, even before he re-aggravtaed his injury in Game 4. Swapping out the Karlsson from Games 1-4 for a healthy, less talented, more defensively sound replacement is probably a downgrade but not a huge one; swapping out the Karlsson from Game 5, when he could barely skate and in retrospect clearly shouldn't have played, is an upgrade.
OTOH, Pavelski and Hertl were their two leading goal-scorers during the regular season and are two of their three best forwards (along with Couture). Hertl in particular would be the biggest loss, because the Sharks don't have a good replacement to center the second line. Thornton centers the third line but he's not a guy who can really play big minutes in the Top 6 or handle tough matchups at this stage of his career (and on the road they can't control matchups). Goodrow centers the fourth line but he's a very limited player who's a useful penalty killer but not much else. I don't think any of their top 9 wingers have much recent experience playing center.
Even without those three guys, though, they should still be able to generate some offense through Couture, Burns, Kane, Meier, Thornton, Labanc. With a more offensively limited lineup it will be harder to dominate for long stretches so the strategy should be to play tighter/smarter defensively, take fewer risks, get a good game from Jones, and hope they get the puck luck to win a 50-50 game. They are certainly underdogs but they aren't out of it yet.