First-team regulars Domenico Criscito, Igor Smolnikov and Danny, as well as Russian Premier League top scorer Hulk, are all banned for the first leg of the last-eight tie.
However, Villas-Boas, whose side sit top of the Russian top flight, was reluctant to discuss how he would cope with the absences following Sunday's 1-1 draw with Rubin Kazan.
"Normally we don't reveal our line-up before," he said. "We have to think hard since we have four players that are suspended and we have to think about the objective. That is for Wednesday."
And the difficulty of the task that lies ahead is not lost on Villas-Boas, who at the time the last-eight draw was made said: "The defending champions is probably the hardest draw we could get.
"Sevilla have quality, experience and recent success in this tournament. All this makes our task even more difficult.
"However, we will play the second leg at home. We will need our fans' support and I am sure they will do their utmost to help us to get through.
"We are ready for these games. We have an aim and a dream, and will give our best to continue to fight for the trophy."
For Sevilla, a meeting with Zenit in the quarter-finals serves as something of a good omen - the La Liga outfit eliminated the Russian club on their way to lifting the trophy back in 2005-06.
And Unai Emery's men return to European action on the back of a morale-boosting 2-2 draw at home to La Liga leaders Barcelona on Saturday.
After falling behind to goals from Lionel Messi and Neymar, Sevilla fought back to achieve a hard-earned point, with Ever Banega and Kevin Gameiro finding the net to restore parity.
Zenit - the only team to have dropped in the Europa League from the Champions League to still be in the competition - have lost all six of their previous games in Spain, while Sevilla are on a seven-match winning run on home soil in European competition.
On the injury front, Zenit are set to be without Viktor Fayzulin (knee), and goalkeeper Beto (hamstring) is a doubt for Sevilla.
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